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Keywords:

  • somite;
  • sclerotome;
  • dermomyotome;
  • myotome

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES

Somites are segments of paraxial mesoderm that give rise to a multitude of tissues in the vertebrate embryo. Many decades of intensive research have provided a wealth of data on the complex molecular interactions leading to the formation of various somitic derivatives. In this review, we focus on the crucial role of the somites in building the body wall and limbs of amniote embryos. We give an overview on the current knowledge on the specification and differentiation of somitic cell lineages leading to the development of the vertebral column, skeletal muscle, connective tissue, meninges, and vessel endothelium, and highlight the importance of the somites in establishing the metameric pattern of the vertebrate body. Developmental Dynamics 236:2382–2396, 2007. © 2007 Wiley-Liss, Inc.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES

Somites are segmental units formed in the paraxial mesoderm on either side of the axial structures, the neural tube and the notochord. They consist of an epithelial wall surrounding a mesenchymal core, the somitocoel cells (Christ and Ordahl, 1995).

The somites arise in a craniocaudal direction budding off from the presomitic mesoderm, which is already epithelialized. The first somite is located behind the otic placode, the last one in the tail. The term “somite” was introduced by Balfour (1881) replacing the former term “Urwirbel” or “Protovertebra” that had been given by Remak (1850) pointing to the role of the somite in vertebral column development, whereas Balfour was mainly considering its attribute as a segmental unit of the embryo.

The structure of avian somites at different stages of maturation was first described by Williams (1910). During development, somites form compartments and subdomains from which various cell lineages derive (Christ et al., 2004; Scaal and Christ, 2004). It has been shown that the early somite consists of pluripotent cells whose specification takes place step by step under the influence of signals emanating from adjacent structures specifying the cells and making up important tissues of the locomotory apparatus of the trunk and the limbs (Jacob et al., 1974; Christ et al., 1992; Ordahl and Le Douarin, 1992; Aoyama 1993) (Table 1). In addition to cell diversification occurring during somite maturation, the somites constitute a metameric pattern within the embryonic body wall that coins the segmental arrangement of the vertebral column, ribs, muscles, tendons, ligaments, dorsal root ganglia, peripheral nerves, and blood vessels (Christ et al., 1972, 1979b, 1998). The metamerism and functional relationship of these structures is the prerequisite for the ability of the vertebrate body to perform bending and rotating movements.

Table 1. Cell Types Originating From Somites
Skeletal muscle cells
Smooth muscle cells
Fibrocytes of connective tissue
Fibrocytes of dermis
Fibrocytes of tendons and ligaments
Adipocytes
Chondrocytes
Osteocytes
Endothelial cells of capillares
Endothelial cells of arteries
Endothelial cells of veins
Endothelial cells of lymphatics
Pericytes
Epineurial cells
Perineurial cells
Fibrocytes of dura mater
Arachnoid cells

In this review, we will show the significance of somites during avian embryogenesis and focus on the derivatives of their compartments as well as on their influence on the establishment of the definitive metameric pattern of the vertebrate body.

SOMITE MATURATION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES

Each somite passes through characteristic steps of maturation showing a posterior to anterior gradient of differentiation, so that the caudalmost somites represent the youngest stages and the oldest stages are gradually aligned more cranially. Accordingly, Christ and Ordahl (1995) proposed a dynamic staging system denominating the youngest somite as somite number I and the cranially abutting somites in consecutive Roman numbers. Up to somites III–IV, somites are organized as epithelial spheres enclosing a lumen, the somitocoel, filled with mesenchymal cells, the somitocoel cells (Fig. 1a). The somite epithelium consists of bottle-like cells extending with their necks to the somitocoel, where they form the apical surface of the epithelium. In the basal compartment, rounded somite cells undergoing mitosis are located between the bottle-like cells (Jacob et al., 1979). Each somite is on its outside covered by a basal lamina, which is connected with adjacent structures by extracellular matrix material (ECM). The basal lamina stabilizes the epithelial structure of the somite. Impairing the cell–ECM interactions by application of synthetic peptides that are blocking receptors involved in this process results in aberrant lobular somite morphology (Jacob et al., 1982). Stereoscanning microscopic studies revealed that the dorsally located epithelial somite cells form cell projections that are contacting the overlying ectoderm (Jacob et al., 1979). Laterally, the somitic epithelium is linked to the lateral plate mesoderm by a continuous cellular bridge, the intermediate mesoderm. The endothelium of the paired dorsal aorta that has originated from the splanchnic mesoderm (splanchnopleure) is closely bordering on the ventral surface of the somite (Christ et al., 1979b).

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Figure 1. Scanning electron micrographs of transverse fractures of an early epithelial somite (A) and a matured somite (B). Note that in the matured somite, the ventral cells have undergone an epithelio-mesenchymal transition to form the sclerotome, whereas the dorsal cells form the epithelial dermomyotome. For definitions of abbreviations, see legend to Figure 4. Reproduced from Christ et al. (2004) with permission of the publisher. Photograph courtesy of Dr. H. J. Jacob, Bochum.

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Figure 4. Schematic representation of the compartments of a young epithelial somite (A, B) and a mature somite (C, D) at the trunk level. A and C are transverse views, B and D are longitudinal views along the section planes indicated by the broken lines in A and C. 1, neural tube; 2, notochord; 3, aorta; 4, surface ectoderm; 5, Wolffian duct; 6, dorsal somite half; 7, ventral somite half; 8, somitocoel cells/arthrotome; 9, central sclerotome; 9a, anterior half of central sclerotome; 9b, posterior half of central sclerotome; 10, ventral sclerotome; 11, lateral sclerotome; 12, dorsal sclerotome; 13, meningeal precursors; 14, axial tendon precursors/syndetome; 15, dermomyotome; 16, epaxial myotome; 17, hypaxial myotome; 18, von Ebner's fissure; 19, spinal nerve.

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Starting at stages IV–V, a morphologically visible dorso-ventral polarization of the somite can be seen leading to two somitic compartments, the dermomyotome and the sclerotome (Fig. 1b). The term “sclerotome” was created by Hatschek (1880) in order to correct the assumption by His (1868) that the cells of this somitic compartment only form the wall of the dorsal aortae, and to highlight its contribution to the axial skeleton.

Sclerotome formation is characterized by an epithelio-mesenchymal transition (EMT) of the ventral half of the somite and the migration of mesenchymal cells under direction of the notochord to form the perinotochordal tissue. This process has been ultrastructurally described by Jacob et al. (1975a, b). The cells extend numerous filopodia and leave the epithelium, keeping their original polarity during emigration (Trelstad, 1977). It is unclear whether EMT depends on signals emanating from the notochord or the ventral neural tube. Christ et al. (1972), Veini and Bellairs (1991), and Hirano et al. (1995) have shown that somites, experimentally separated from both the notochord and the neural tube nevertheless show dissociation of the ventral somite wall forming a sclerotome-like structure in which, however, cell number is considerably reduced. On the other hand, it has been shown that the dorsal half of the somite, which normally retains its epithelial structure, can be forced to undergo EMT under the influence of experimentally intensified notochordal signals (Brand-Saberi et al., 1993).

The maintenance of the epithelial structure of the dorsal epithelial somite, which constitutes the dermomyotome, depends on Wnt-6 expressed in the overlying ectoderm. Wnt-6 was shown to be required for the expression of the epithelialization factor Paraxis in the paraxial mesoderm and for the formation and maintenance of somite epithelium (Burgess et al., 1996; Sosic et al., 1997; Rodriguez-Niedenführ et al., 2003; Schmidt et al., 2004a, b; Linker et al., 2005). In the mature dermomyotome, the medial and lateral lips of the dermomyotome are maintained under the influence of dermomyotomal Wnt-11 and ectodermal Wnt-6, respectively, whereas the central dermomyotome deepithelializes to give rise to muscle and dermis (Geetha-Loganathan et al., 2006).

In the sclerotome, the EMT is accompanied by a down-regulation of N-cadherin leading to a decrease in cell adhesion and an increase in cell motility (Hatta et al., 1987; Sosic et al., 1997; Duband et al., 1987; Takeichi, 1988). The sclerotome is defined not only by its mesenchymal organization but also by the expression of sclerotome-specific marker genes, such as Pax1 and Pax9 (Dietrich et al., 1993; Koseki et al., 1993; Peters et al., 1995). Pax1 expression precedes the EMT (Müller et al., 1996) and both genes are induced by notochordal signals (Ebensperger et al., 1995) that have been identified as Shh and Noggin cooperating during sclerotome formation (Fan and Tessier-Lavigne, 1994; Johnson et al., 1994; McMahon et al., 1998; reviewed by Dockter, 2000, and Christ et al., 2004).

During growth of the embryo and further maturation of the somites, various sclerotomal subdomains appear that give rise to different structures. Pax1 expression is down-regulated in the dorsal and lateral parts of the sclerotome that develop independently of notochordal signals (Ebensperger et al., 1995; Monsoro-Burq et al., 1996; Monsoro-Burq and Le Douarin, 2000) (Fig. 2). The central part of the sclerotome is located close to the myotome and reveals high cell density. Huang et al. (2003a, b) concluded that this part of the sclerotome develops under the influence of Fgfs produced by a subpopulation of myotomal cells. The ventral part of the sclerotome develops around the notochord and gives rise to vertebral bodies and intervertebral discs (Hall, 1977; Wallin et al., 1994; Christ et al., 1979b, 1998, 2000). Close to the lateral surface of the neural tube, a medial subdomain arises that gives rise to the blood vessels and meninges of the spinal cord (Kurz et al., 1996; Halata et al., 1990; Nimmagadda et al., 2004, 2005, 2007). An additional subdomain of the sclerotome is formed by the somitocoel cells (Huang et al., 1994, 1996; Mitapalli et al., 2005), which specifically contribute to the articulations of the vertebral column.

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Figure 2. Transverse section of a mature somite of a 3-day chick embryo. In situ hybridization against Pax1 shows that Pax1 expression is absent in the dorsal and lateral sclerotome (arrows). Reproduced from Christ et al. (2004) with permission of the publisher.

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After formation of the sclerotome, the dorsal epithelium is now commonly referred to as the dermomyotome reflecting the main future fates of these cells as myogenic and dermogenic precursors. In a dorsolateral view, the dermomyotome appears almost square. Its borders bend in to form lip-like structures that are important for the formation of the third compartment of the somite, the myotome (Christ et al., 1978b; Kaehn et al., 1988; Denetclaw et al., 1997; Kahane et al., 1998a, b; reviewed in Brent and Tabin, 2002). Pax3 and Pax7 are marker genes of the dermomyotomal cells whereas the myotomal cells express muscle regulatory factors (MDFs) (Ott et al., 1991; Pownall and Emerson, 1992; reviewed in Stockdale et al., 2000).

Once the myotome begins to form, the remaining somite epithelium has often been termed the “dermatome,” implying that the cells of this layer are destined to form only dermal cells. It is well known today that this epithelium (“epithelial plate” according to Fischel, 1895) contains precursors for both muscle and dermis and should be better termed “dermomyotome” as was suggested by Christ and Ordahl (1995). During its later stages of development, the dermomyotome epithelium undergoes an EMT giving rise to myoblasts and dermoblasts (Gros et al., 2005; Kalcheim et al., 2006). Prior to the dissociation of the dermomyotome, the orientation of the mitotic spindles in the dermomyotomal sheet shifts from a parallel to a perpendicular orientation relocating the daughter cells dorsally to form dermis and ventrally to contribute to muscle. The distribution and fate of the daughter cells is suggested to be controlled by N-cadherin (Ben-Yair and Kalcheim, 2005).

ANTERIOR-POSTERIOR POLARIZATION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES

In addition to the somite compartments visible on transverse sections, the somites become subdivided in an anterior half and a posterior half (Remak 1850; von Ebner, 1888; reviewed in Brand-Saberi and Christ, 2000). This anterior-posterior polarization becomes morphologically visible within the sclerotome dividing it into two halves that are separated by the intervertebral fissure (v. Ebner's fissure) in which the sclerotomal cells are elongated and transversally oriented (Christ et al., 1979b). Both halves of the sclerotome differ with respect to cell density, produced proteins, and the behavior of migrating neural crest cells and outgrowing axons. Neural crest cells and axons exclusively invade the cranial half of the sclerotome, whereas the caudal half has a repellent influence on them (Rickmann et al., 1985; Keynes and Stern, 1984; Bronner-Fraser, 1986; Teillet et al., 1987). This somitic polarity is initiated before somite formation in the presomitic mesoderm. Its formation and maintenance is controlled by the Delta-Notch signaling pathway interacting with the basic helix-loop-helix transcription factor Mesp2 (Del Amo et al., 1992; Hrabe de Angelis et al., 1997; Jen et al., 1997; del Barco Barrantes et al., 1999; Saga and Takeda, 2001). Ephrins have been shown to be responsible for the repellent property of the posterior half-sclerotome. In the chick embryo, Ephrin B1 and B4 are expressed in the posterior sclerotome and repel motor axons (Wang and Anderson, 1997). Corresponding receptors for the ephrins, EphB2 and EphB3, are present on the motoneuron axons restricting their outgrowth to the cranial half-sclerotome (Henkemeyer et al., 1994; Ohta et al., 1996; Robinson et al., 1997). This anterior-to-posterior subdivision of the sclerotome is maintained by signals from the neural tube and possibly from the ectoderm (Schmidt et al., 2001; Schrägle et al., 2004; Colbjorn Larsen et al., 2006). Recent studies have shown TGF-beta Type II receptor (Tgfbr2) to be involved in the maintenance of sclerotome boundaries that are required for the segmental pattern of the peripheral nervous system and the morphogenesis of the vertebral column (Christ and Wilting, 1992; Huang et al., 2000b; Christ et al., 2000; Baffi et al., 2006).

AXIAL IDENTITIES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES

Vertebrae at different levels show distinct morphological features allowing discrimination, for instance, between cervical and thoracic vertebrae. This segment specificity is already determined in the presomitic mesoderm. After heterotopic grafting of presomitic mesoderm from the prospective thoracic region into cervical or lumbosacral regions, ectopic ribs develop (Kieny et al., 1972; Jacob et al., 1975a). This segment-specific identity is achieved by functions of the Hox gene family. Four clusters of Hox genes can be distinguished, each of them located on another chromosome. Single Hox genes are activated along the body axis corresponding to their serial arrangement within the Hox complex, a phenomenon called “colinearity” (Duboule and Dollé, 1989; Graham et al., 1989; Krumlauf, 1994). Every segment is characterized by a local combination of Hox gene expressions, thus creating a segment-specific Hox-code that specifies the axial identities of somites and somite derivatives (Kessel and Gruss, 1991; reviewed in Kmita and Duboule, 2003). Heterotopic grafting experiments have shown that cells from all compartments of the somite form skeletal structures according to their original positional information by maintaining the original Hox gene expression within the new environment (Nowicki and Burke, 2000; Dieuguie Fomenou et al., 2005). Hypaxial muscle formation at the limb level was found to be controlled by the somatic mesoderm and not by the somite-derived muscle precursors (Christ et al., 1977, 1979c; Alvares et al., 2003). Murakami and Nakamura (1991) as well as Alvares et al. (2003) have shown that thoracic and cervical somites grafted at the non-limb level are predisposed towards a particular myogenic program.

DEVELOPMENT OF THE VERTEBRAL COLUMN

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES

The formation of anterior and posterior sclerotome halves is indispensable for the development of the metameric vertebral column. The posterior half-sclerotome, for example, is characterized by the expression of the homeobox gene Uncx4.1 (Mansouri et al., 2000; Leitges et al., 2000; Schrägle et al., 2004). In homozygous Uncx4.1 mutant mice, the pedicles, proximal ribs, and transverse processes of the vertebrae are lacking, indicating that both halves of the sclerotome differ with respect to their function in vertebra formation. It has become quite clear that the boundaries of vertebrae are shifted one half segment as compared to somite boundaries (Bagnall et al., 1988, 1989; Huang et al., 1996, 2000a,b; reviewed in Christ et al., 2000). The transition from somites to vertebrae can be described as a process of “resegmentation.” In older articles, the somites have been called “protovertebrae” relating them to the vertebrae, the definitive structures of the vertebral column (Remak, 1850; Corning, 1881). Recent molecular studies have shown that resegmentation is highly conserved in evolution (reviewed in Christ et al., 1998). The extent of contribution of both halves of the sclerotome to the vertebrae considerably differs. The posterior half, which is the main provider of vertebral precursor cells, gives rise to the intervertebral tissue, the transverse processes, the costal head, and the intervertebral joints. In the middle of the rib, a boundary between the anterior and posterior part of adjacent somites exists, whereas in the distal part of the rib, the cells derived from both sclerotome halves gradually mix, indicating that segmentation is lost in the ventral body wall (Huang et al., 2000a,b). One somite provides the material for one segmental muscle including its skeletal attachments, meaning that during resegmentation the segmental muscle rudiments carry with them their origin and insertion, as was also shown for the branchial muscles (Köntges and Lumsden, 1996).

Due to gradients of different signaling molecules in dorso-ventral and medio-lateral directions, various subdomains of the sclerotome appear. The central part of the sclerotome is located close to the myotome, the ventral part is formed by the invasion of Pax1-expressing cells from the ventromedial edge of the very early sclerotome (Table 2, Fig. 2). The Pax1-negative cells in the dorso-medial angle of the sclerotome migrate in a dorso-medial direction to form the dorsal sclerotome whose cells express Msx1 and Msx2 (Monsoro-Burq et al., 1994). Cells of this subdomain form the dorsal part of the neural arch and the spinous process under the control of BMP4 produced by the roof plate of the neural tube and possibly by the surface ectoderm (reviewed in Monsoro-Burq and Le Douarin, 2000). Interruption of this cross-talk could be one of the reasons that cause spina bifida.

Table 2. Sclerotomal Subdomains and Their Derivatives
Sclerotome subdomainDerivatives
Central sclerotomePedicle part of neural arch, proximal rib, syndetome
Ventral sclerotomeVertebral body, intervertebral disc
Dorsal sclerotomeDorsal part of the neural arch, spinous process
Lateral sclerotomeEndothelial cells, distal rib, tendons
Medial sclerotomeMeninges of the spinal cord, blood vessels
Somitocoel cellsVertebral joints, intervertebral discs, proximal ribs
Anterior halfVertebral body, perineurium, small part of the neural arch, endoneurium, small part of the distal rib
Posterior halfVertebral body, transverse process, proximal part of the rib, main part of the distal rib, main part of the neural arch

The differentiation of cells in the lateral sclerotome seems to be dependent on Fgfs from the overlying myotome and on BMP4 from the lateral plate mesoderm (Pourquié et al., 1995, 1996). This sclerotomal subdomain gives rise to distal ribs and contributes to tendons (Huang et al., 1994, 2000a, 2003a, b; Olivera-Martinez et al., 2000; Brent et al., 2003). The function of the lateral sclerotome to form blood vessels will be discussed later.

The central part of the sclerotome develops in close contact to the myotome whose cells produce Fgfs under the control of ventral axial structures (Stolte et al., 2002; Huang et al., 2003a, b). It is characterized by densely packed cells and is triangular in shape when studied on transverse sections through the posterior half of the sclerotome. It mainly gives rise to the ventral part of the neural arches and the edges of the triangle represent the rudiments of the intermediate part of the neural arch, the rib (or rib-homologous structure), and the pedicle (Christ et al., 1979b, 1992).

The ventral subdomain of the sclerotome is formed by cells migrating into the initially cell-free perinotochordal space (Jacob et al., 1975a, b). These immigrating cells there proliferate to form the perinotochordal tube (Töndury, 1958) from which the vertebral bodies and intervertebral discs arise. The invasion of the perinotochordal space by sclerotomal cells and their proliferation depend on signals that emanate from the notochord. Shh, Noggin, and Fgf8 have been identified to control the expression of Pax1, Pax9, Twist, and Mfh1 in sclerotomal cells promoting their proliferation (Chen and Behringer, 1995; Wallin et al., 1994; Ebensperger et al., 1995; Miura et al., 1993; Neubüser et al., 1995; Kaestner et al., 1996; Winnier et al., 1997; Christ et al., 2000; Müller et al., 1996; Hornik et al., 2004). The ventral sclerotome forms vertebral bodies and intervertebral discs. The discs show high mitotic activity providing the adjacent vertebral bodies, whose cells begin to differentiate very early, with additional cells, and thus function as growth centers of the vertebral column (Wilting et al., 1994). There is a cross-talk between the notochord and the cells of the ventral sclerotome, since Pax1-deficient mice lacking a differentiation of the ventral sclerotome have an enlarged notochord (Wallin et al., 1994). In Pax1/Pax9 double mutant mice, the derivatives of the ventral sclerotome are completely missing (Peters et al., 1999).

Of special interest are the somitocoel cells. After sclerotome formation. they are integrated into the posterior half of the sclerotome close to the intervertebral (von Ebner's) fissure (Huang et al., 1994, 1996). Here they form a triangular area, with its tip reaching to the notochord, along the border of the anterior and posterior sclerotome halves, thus forming the boundaries of the vertebral motion segment (Fig. 3). The somitocoel cells give rise to the vertebral joints, intervertebral discs, and proximal ribs (Bagnall et al., 1998, 1989, Huang et al., 1994, 1996). Microsurgical removal of these cells leads to loss of vertebral joint formation and fusion of the articular processes and vertebral bodies. The somitocoel cells and its derivatives have, therefore, been called “arthrotome” (Mittapalli et al., 2005).

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Figure 3. Coronal section of a 4-day chick embryo showing the location of the arthrotome after homotopic transplantation of quail somitocoel cells into a chick embryo. Arthrotome cells are stained with QCPN antibody (arrow). For definition of abbreviations, see legend to Figure 4.

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Special subdomains of the sclerotome have been termed “syndetome” because their cells give rise to the tendons that connect the epaxial muscles with the vertebrae (Brent et al., 2003). Each of them is located at the anterior and posterior border of the sclerotome adjacent to the myotome. The cells of this subdomain express scleraxis under the control of Fgf8 produced by myotomal cells. Fgf8 binds to the Fgf receptor, FREK, which is only expressed in myotomal cells that are located at the anterior and posterior border of the myotomes and emanate a signal that is required for scleraxis activation (Brent et al., 2003). The expression of myotomal Fgf8 was found to be regulated by the ventral axial structures (Huang et al., 2003). In a recent study, Brent et al. (2005) have shown that axial tendon and cartilage-forming cells are alternative lineages, since chondrogenesis represses tendon development in the dorsolateral sclerotome.

Chondrogenic differentiation of sclerotomal cells depends on the expression of the homeobox gene Bapx1 (Murtaugh et al., 1999, 2001). Meox proteins are required for Bapx1 expression (Rodrigo et al., 2004) and Bapx1 is a direct target of Pax1 and Pax9 (Rodrigo et al., 2003). Other genes that are involved in the control of chondrogenesis are Col2 encoding collagen II and its transcriptional activator Sox9 (Bell et al., 1997; Healy et al., 1996; Bi et al., 2001). In addition to its cartilage-forming function, Sox9 is required for notochord survival (Barrionuevo et al., 2006).

MUSCLE

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES

All skeletal muscles of the vertebrate body originate from the dermomyotome with the exception of head muscles (reviewed in Scaal and Christ, 2004). The dermomyotome is formed after sclerotome formation by the remaining somite epithelium beneath the surface ectoderm. The dermomyotomal fate is determined and maintained by dorsalizing signals from adjacent structures. These signals are Wnts secreted by the dorsal neural tube (Wnt1 and Wnt3a) and the surface ectoderm (Wnt6) (Spence et al., 1996; Dietrich et al., 1997; Fan et al., 1997; Marcelle et al., 1997; Capdevila et al., 1998; Ikeya and Takada, 1998; Wagner et al., 2000; Rodriguez-Niedenführ et al., 2003). Molecular markers of the dermomyotome include Pax3 and Pax7 (reviewed in Stockdale et al., 2000). Pax3, which is first expressed in the cranial part of the presomitic mesoderm, becomes down-regulated in the ventral half of the somite and the somitocoel cells during sclerotome formation, ultimately becoming restricted to the dorso-medial and ventro-lateral lips of the dermomyotome.

Muscle is phylogenetically the oldest derivative of the somite (reviewed in Brand-Saberi and Christ, 2000). Still in recent fishes, the myotome represents the largest and earliest formed somitic domain (reviewed in Brennan et al., 2002). In the avian embryo, the muscle compartment can be experimentally enlarged at the expense of the skeleton-forming compartment by an increase of Wnt signaling (Wagner et al., 2000).

The paraxial mesoderm is specified to form muscle by signaling molecules from adjacent structures. It has been shown by ablation experiments in the avian embryo that the neural tube, the surface ectoderm, and the notochord-floor plate-complex are involved in the induction of myogenesis (Christ et al., 1992; Rong et al., 1992; Bormann and Yorde, 1994; Buffinger and Stockdale, 1994; Stern and Hauschka, 1995; Cossu et al., 1996; Geetha-Loganathan et al., 2005).

The first molecular manifestation of muscle differentiation is the expression of MRFs (muscle regulatory factors). In the avian embryo, the first known MRF to be expressed is MyoD followed by Myf5 (reviewed in Stockdale et al., 2000). Double mutant mice for these two MRFs lack all skeletal muscles (Rudnicki et al., 1993). A balanced signaling of Shh from the notochord/floor plate complex and Wnts from the dorsal neural tube acts to initiate myogenesis (Münsterberg et al., 1995; Münsterberg and Lassar, 1995). Myogenesis is negatively regulated by BMPs (Pourquié et al., 1996). Thus, the onset of myogenesis in the medial part of the dermomyotome is accompanied by the production of the BMP-antagonist Noggin in the dorsomedial somite (Reshef et al., 1998).

The muscles originating from the dermomyotome can be assigned as epaxial muscles of the back and as hypaxial muscles of the ventro-lateral body wall and the limbs. The epaxial muscles originate from the medial half of the epithelial somites, the hypaxial muscles from to the lateral half (Ordahl and Le Douarin, 1992). The hypaxial muscle differs in the modality of origin (reviewed in Christ and Ordahl, 1995). At limb level, cells of the lateral dermomyotome deepithelialize and migrate as single or groups of Pax3, Lbx1, Six1/Six4-expressing cells into the limb buds to form limb-specific muscle blastemata (Christ et al., 1974a, 1977; Jacob et al., 1978, 1979; Brohmann et al., 2000; Grifone et al., 2005; reviewed in Vasyutina and Birchmeier, 2006). Deepithelialization of the muscle precursors is induced by Scatter factor (SF)/HGF, that is being secreted by lateral plate mesodermal cells at the basis of the limb anlagen (Bladt et al., 1995; Brand-Saberi et al., 1996a; Scaal et al., 1999). Mice lacking SF/HGF or its receptor c-met lack limb muscle. At interlimb level, epithelial “somitic buds” invade the somitic mesoderm giving rise to abdominal and intercostal muscles (Christ et al., 1978a, b, 1983). Similar to the situation at limb level, a population of migrating muscle precursor cells detaches from the lateral dermomyotomes of the somites 2–6 and migrate into the tongue rudiment and the neck to form glossal and infrahyoid muscles (Schemainda 1981, Huang et al., 1999, 2001).

From premuscular masses located in the proximal limb buds, cohorts of MyoD-expressing cells move caudally and/or proximally and leave the limb to form perineal and pectoral girdle muscles. This mode of muscle translocation has been termed an “in-out” mechanism by Valasek et al. (2005) (reviewed in Evans et al., 2006).

The back muscles originate from the medial part of the dermomyotome. The mechanisms of myotomal cell recruitment have been studied in detail during the last two decades (Kaehn et al., 1988; Denetclaw et al., 1997, 2001; Kahane et al., 1998, 2001; Huang and Christ, 2000; Gros et al., 2004). It has been shown that in a first step, myotomal cells are provided by the dorsomedial lip of the dermomyotome by ingression and bidirectional extension. In a second step, the anterior, posterior and lateral dermomyotomal lips also start to release myotomal precursor cells, as was suggested previously by Christ et al. (1978b). The early back muscles are segmentally arranged. Later their superficial parts fuse to form segment-overbridging muscles, a process that is not well understood to date.

Each hypaxial muscle can be recognized by its specific shape and structure that were found to be determined by local cues coming from the somatic mesoderm (Christ et al., 1979a, b; Christ and Jacob, 1986; Jacob et al., 1982; Kardon, 1998; Kardon et al., 2002, 2003). This is also the case for muscle size (reviewed in Patel et al., 2002). In addition, recent studies have demonstrated that the myogenic adult progenitor cells, satellite and side population cells, are of somitic origin (Gros et al., 2005, Schienda et al., 2006).

The relationship between single somites and muscles has been studied at the occipital and cervical levels as well as at the wing level (Huang et al., 2000a,b; Zhi et al., 1996) and leg level (Lance-Jones, 1988; Rees et al., 2003) and is exemplarily summarized for individual forearm and hand muscles in Table 3.

Table 3. Contributions of Individual Somites to Brachial Musclesa
MuscleSomites
161718192021
  • a

    Adopted from Zhi et al. (1996).

Dorsal group of the forearm      
 M. extensor medius longus  
 M. extensor indicis longus  
 M. extensor metacarpi radialis   
 M. extensor digitorum communis   
 M. anconeus  
 M. extensor metacarpi ulnaris   
Ventral group of the forearm      
 M. ulnimetacarpalis ventralis
 M. flexor digitorum profundus  
 M. flexor digitorum superficialis   
 M. flexor carpi ulnaris 
 M. pronator profundus   
 M. pronator superficialis   
Dorsal group of the hand      
 M. extensor indicis brevis/M. abductor indicis 
 M. extensor medius brevis 
 M. interosseus dorsalis 
Ventral group of the hand      
 M. flexor indicis/M. abductor indicis 
 M. abductor medius 
 M. interosseus palmaris 
 M. flexor digiti IV/M. ulnimetacarpalis dorsalis

DERMIS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES

Somites contribute only to the dermis of the back while the dermis of the ventro-lateral body wall originates from the somatopleure (Mauger, 1972; Christ et al., 1983; Zhi et al., 1996). There is a sharp boundary between somite-derived and somatopleure-derived dermis, which corresponds to the lateral somitic frontier described by Ann Burke and colleagues (Nowicki et al., 2003; Burke and Nowicki, 2003). Regarding the contribution of the somites to the dorsal dermis, Olivera-Martinez et al. (2000) came to the conclusion that dermis cells derive only from the medial half of the somite. The subcutis underlying the dermis, which is also of somitic origin, was found to behave likewise. This view has been challenged by Ben-Yair et al. (2003) by suggesting that the entire mediolateral extent of the dermomyotome contributes to the formation of the lack dermis. By clonal analysis of the central part of the dermomyotome, it has been shown that single dermomyotomal cells give rise to both dermis and muscle during the EMT of the dermomyotome epithelium, suggesting that the dermomyotome must contain at least bipotent progenitors (Ben-Yair and Kalcheim, 2005). According to Le Lièvre and Le Douarin (1975), the dermis of the head and partly of the neck is formed by neural crest cells.

ANGIOGENESIS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES

The basic structure of blood vessels (arteriae and veins) is characterized by an inner lining of endothelial cells and a wall consisting of pericytes, smooth muscle cells, and fibrocytes. Angioblasts, the precursors of endothelial cells, arrange as cords that undergo tubulogenesis to form a lumen. In addition to the splanchnic mesoderm, the somites have been identified to be important sources of angioblasts (Christ, 1969; Wilting et al., 1995b; Pardanaud and Dieterlen-Lièvre. 1993; Pardanaud et al., 1996). Angioblasts and endothelial cells can be identified by the expression of VEGFR-2 (Quek1) in the quail embryo (Eichmann et al., 1993). VEGFR-2 is expressed in the lateral parts of the epithelial somite, the dermomyotome and the sclerotome (Wilting et al., 2003; reviewed in Wilting and Becker, 2006). However, quail-chick grafting experiments have shown that all compartments of the maturating somite have the capacity to form endothelial cells (Wilting et al., 1995b). According to their location in the somite, angioblasts preferentially populate certain body regions. The ventral half-somite gives rise to the endothelium of ventro-lateral blood vessels. Within the dermomyotome, angioblasts from the dorso-medial quadrant migrate predominantly into the dorsal dermis, and angioblasts from the dorso-lateral quadrant populate the ventrolateral body wall and the limbs (Wilting et al., 1995b). Somite-derived angioblasts normally do not cross the midline of the embryo. It is the notochord that has been identified to keep endothelial precursor cells from migrating to the controlateral side (Klessinger and Christ, 1996). It is likely that the repulsive effect of the notochord on migrating angioblasts is mediated by Noggin (Nimmagadda et al., 2005). Recent studies have revealed that the angioblastic capacity of the somites is balanced, on the one hand, by BMP4 expressed in the lateral plate mesoderm and later in the dorsal part of the neural tube and, on the other hand, by Noggin expressed in the notochord (Nimmagadda et al., 2005). In addition, Fgfs and Wnts modulate the capacity to form endothelial cells (Nimmagadda et al., 2007). Huang et al. (2003b) have shown that somites 16–21 give rise to endothelial cells of the wing. Interestingly, there is no strict correlation between the distribution of muscle and endothelial cells from a single somite indicating that myoblasts and angioblasts derived from the same somite migrate on different routes in the developing wing bud. The origin and migration of angioblasts from the somites does not require an interaction of SF (HGF) and c-met because at interlimb level, where there is no detachment of muscle precursor cells from the dermomyotome, endothelial cells still invade the abdominal wall (Christ et al., 1979a; Wilting et al., 1995b).

Somites not only give rise to endothelial cells but also have the capacity to invest differentiating vessels by periendothelial cells, which give rise to pericytes, smooth muscle cells, and fibrocytes (reviewed in Brand-Saberi and Christ, 2000). The somitic origin of smooth muscle cells in the dorsal aorta was recently demonstrated in the chick embryo (Pouget et al., 2006). Esner et al. (2006) have shown that in the mouse embryo, smooth muscle cells of the dorsal aorta share a common clonal origin with skeletal muscle cells of the myotome.

The somites also give rise to lymphatic endothelial cells of which the precursors can be identified with specific markers, such as Prox1 (Wilting and Becker, 2006). Scattered Prox1-positive cells are present in the dermomyotome of the chick from 3.5 day onwards. In quail embryos, these cells co-express the endothelial marker QH1 (reviewed in Wilting and Becker, 2006). These dermomyotomal lymphangioblasts are suggested to form the lymphatics of the dorsal skin and the limbs (Wilting et al., 2000; He et al., 2003).

THORACIC AND ABDOMINAL WALL

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES

The thoracic wall is characterized by the sternum as well as segmentally arranged ribs and intercostal muscles, while the abdominal wall contains segment-overbridging abdominal muscles and tendons. The somatopleure functions as the matrix of the entire ventro-lateral body wall and forms connective tissue, flat tendons, and the sternum (Fell 1939, Christ et al., 1974b, 1983; Chevallier, 1979). The ribs undergo resegmentation and grow as ventral processes of the sclerotomes into the somatic mesoderm up to the originally paired sternal plates, which move ventrally and eventually fuse (Christ et al., 1974b; Huang et al., 2000a,b; Evans, 2003). The development of the sternal parts of the ribs requires inductive signals from the somatopleure which are mediated by BMPs (Sudo et al., 2001). The intercostal muscles derive from somites 19–26 (Chevallier, 1975; Evans, 2003). According to Aoyama et al. (2005), each rib consists of three compartments: The development of the proximal rib depends on signals from the notochord/floor-plate-complex, the distal rib on signals from the ectoderm, and the sternal (i.e., distalmost) part on signals from the lateral plate mesoderm. The intercostal muscles develop in close relationship with the ribs, each of them originating as extensions from one dermomyotome. The cross-talk between these two somitic derivatives, rib and intercostal muscle, is not well understood to date (Evans et al., 2006).

The muscles of the abdominal wall include the external and internal obliques abdominis, the transverse abdominis, and the rectus abdominis, the latter being the ventralmost one. The development of these muscles in the chick was studied in detail by Christ et al. (1983). The lateral part of dermomyotomes and myotomes grow as epithelial “somitic buds” into the somatopleure. In day-5 embryos, these buds lose their epithelial structure by EMT on either side and form a premuscular mass that is not longer segmentally organized. It seems that myogenic cells migrate from this premuscular masses anteriorly to form the rectus abdominis muscle (reviewed in Evans et al., 2006). It has to be added that most of the endothelial cells lining the blood vessels within the ventrolateral body wall are derived from the somites.

LIMB AND LIMB GIRDLE

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES

Early limb anlagen are thickenings of the somatopleure covered by surface ectoderm. The complex signaling pathways controlling the initiation and specification of limbs require inductive cues from the presomitic mesoderm. After separation of the somatopleure from the paraxial mesoderm by insertion of a barrier at limb level, limbs do not develop (Christ and Jacob, 1986).

As described earlier, the somites provide the limbs with myoblasts and angioblasts that become integrated in limb-specific muscles and a vascular pattern that are controlled by the somatopleure-derived limb mesoderm (reviewed in Brand-Saberi and Christ, 1999; Evans et al., 2006). Whereas the somatopleure does not form skeletal muscle cells (Wachtler et al., 1982), it can give rise to endothelial cells and thus compensate for lacking somite-derived endothelial cells. Lymphangioblasts also invade the limb buds where they form lymphatic vessels (Schneider et al., 1999; Wilting et al., 2000; He et al., 2003).

The onset of myoblast migration depends on the expression of Lbx1. In Lbx1-mutant mice, the muscle precursor cells are unable to form a dorsal premuscular mass in the limb while the migration to the ventral premuscular mass seems to be unaffected (Brohmann et al., 2000; Gross et al., 2000). The muscle precursor cells are guided on their routes by signals from the limb mesoderm including SF/HGF (Dietrich et al., 1999; Scaal et al., 1999) and N-Cadherin (Brand-Saberi et al., 1996). After reaching their destination, the myoblasts stop to proliferate, downregulate the Wnt antagonist Sfrp2 (Anakwe et al., 2003), and activate the myogenic program via Myf5 and MyoD to express Myogenin, Mef2, and MRF4 (reviewed in Buckingham et al., 2006). The realization of this program is influenced by ectodermal Wnt6 that promotes Myf5- dependent avian limb myogenesis (Geetha-Loganathan et al., 2005).

The limbs are linked to the trunk via shoulder and pelvic girdles composed of several skeletal elements, muscles, and ligaments. Most of the girdle skeleton is formed by the lateral plate mesoderm. Considering avian scapula formation, Chevallier et al. (1977) obtained experimental evidence that the somites contribute to scapula development. Studying different vertebrate species, Burke (1991) also came to the conclusion that the somites can be a source of scapula-forming cells. This was confirmed and more precisely defined in the chicken embryo by Huang et al. (2000c), Ehehalt et al. (2004), and Wang et al. (2005) who showed that while the scapula head and column originate from lateral plate mesoderm, the long blade of the avian scapula is formed by somites 17–24 and shows a segmental organization. Additionally, they showed that the dermomyotomes but not the sclerotomes of these somites give rise to the scapula blade showing that at least lateral dermomyotomal cells of the somites 17–24 have a chondrogenic potential. It has been demonstrated that BMP signals derived from lateral plate mesoderm and as yet unidentified signals from the ectoderm are required to activate this intrinsic, segment-specific chondrogenic program (reviewed in Huang et al., 2006).

In contrast to the development of the shoulder girdle, all skeletal elements of the pelvic girdle are derived from lateral plate mesoderm and their development is controlled by not yet identified ectodermal signals (Malashichev et al., 2005).

SPINAL CORD AND MENINGES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES

The development of the spinal cord requires the blood vessel–forming potential of the adjacent somites. The developing neural tube is avascular. During the third day of development, VEGFR-2 (Quek-1) becomes expressed in the medialmost subdomain of the sclerotome that surrounds the neural tube and forms the perineural vascular plexus (Nimmagadda et al., 2004). It is induced by BMP4 expressed in the dorsal neural tube after downregulation of notochordal Noggin (Nimmagadda et al., 2005). The formation of this medial subdomain of the sclerotome is, furthermore, positively controlled by VEGFA emanating from the neural tube. Not only the blood vessels but also the meninges of the spinal cord are formed by the medial sclerotome (Halata et al., 1990). The primitive meninx becomes subdivided into two layers, the ectomeninx and the endomeninx, forming the dura mater, the inner and outer arachnoid layers, and the pial layer. The neural tube becomes vascularized from the perineural plexus by invasion of capillary sprouts (Kurz et al., 1996), while the pericytes and vascular smooth muscle cells were found to be of neuroectodermal origin (Korn et al., 2002).

PERSPECTIVES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES

In this brief overview, we have highlighted the central role of the somites for the development of a diversity of mesodermal structures that compose the functional body wall of amniote species. The somites can be considered as a stem cell pool of primarily multipotent cells that are fated into divergent developmental lineages by a complex and tightly regulated network of signaling cues. Most of these signals emanate from neighboring structures and act on the somite cells over considerable distances. Thus, the intimate interrelation of skeleton, musculature, vasculature, and nervous system that provides the functionality of the vertebrate body is reflected by the tight and intricate interaction of the somite with its embryonic environment during development. We are only scratching the surface of the incredibly precise and reliable molecular machinery that instructs individual somitic cells to play their part in the developing organism. Much further effort will be needed to better understand how the somites build the vertebrate body wall.

Acknowledgements

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES

We thank Dr. Suresh Nimmagadda for help with the figures and Ulrike Uhl for typing the manuscript. Figures 1 and 2 have been adopted and modified from Christ et al. (2004) with kind permission from Springer Verlag, Heidelberg. We thank the Deutsche Forschungsgemeinschaft (SFB 592, GRK 1104, Hu729/2) and the European Network of Excellence MYORES for financial support.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SOMITE MATURATION
  5. ANTERIOR-POSTERIOR POLARIZATION
  6. AXIAL IDENTITIES
  7. DEVELOPMENT OF THE VERTEBRAL COLUMN
  8. MUSCLE
  9. DERMIS
  10. ANGIOGENESIS
  11. THORACIC AND ABDOMINAL WALL
  12. LIMB AND LIMB GIRDLE
  13. SPINAL CORD AND MENINGES
  14. PERSPECTIVES
  15. Acknowledgements
  16. REFERENCES