“Highlights” calls attention to exciting advances in developmental biology that have recently been reported in Developmental Dynamics. Development is a broad field encompassing many important areas. To reflect this fact, the section will spotlight significant discoveries that occur across the entire spectrum of developmental events and problems: from new experimental approaches, to novel interpretations of results, to noteworthy findings utilizing different developmental organisms.
Mother of invention (Apical Polarity Protein PrkCi Is Necessary for Maintenance of Spinal Cord Precursors in Zebrafish by Randolph K. Roberts and Bruce Appel, Dev Dyn238:1638–1648) It's inevitable that a daughter will want to be different from her mother. In Drosophila, an apical Par polarity complex containing atypical protein kinase C (aPKC) guides asymmetric division of neuroblasts, endowing daughter cells with characteristics needed to adopt different fates. Here the authors confirm that, unlike in Drosophila, zebrafish CNS neuroblasts do not reorient their plane of cell division during neurogenesis, calling into question whether vertebrates need apicobasal polarity cues to generate asymmetric divisions. This notion was tested by analyzing heart and soul (has) mutants with disrupted zygotic protein kinase C, iota (PrkCi), an aPKC isoform. The authors find that some has mutant neuroblasts lose expression of an apical neuroepithelial adherens junctions marker over time, and the neural tube central canal is discontinuous, both demonstrating that neuroepithelia break down. In addition, while wild-type (wt) cells divide planar relative to neuroepithelia, has−/− cells divide obliquely. PrkCi cells, then, lose signs of apicobasal polarity, but is cell fate impacted? The has−/− cells near the central canal prematurely cease expression of spinal cord precursor markers, and embryos exhibit a 1.4-fold overabundance of oligodendrocytes. Supporting the conclusion that increased oligodendrocytes is due to misspecification of spinal cord precursors and not overproliferation, the net number of mitotic precursors are equivalent in wt and has−/− embryos over time. Therefore, PrkCi appears to regulate asymmetric divisions in vertebrates, but It remains a mystery how this is accomplished without reorientation of the plane of division. A good mother will do whatever it takes to help her daughters be who they want.
Pig in a poke (Depigmentation of Skin and Hair Color in the Somatic Cell Cloned Pig by Kyu-Chan Hwang, Seong-Keun Cho, Seong-Hoon Lee, Jong-Yi Park, Deug-Nam Kwon, Yun-Jung Choi, Chankyu Park, Jae-Hwan Kim, Keun-Kyu Park, Seongsoo Hwang, Soo-Bong Park, and Jin-Hoi Kim, Dev Dyn238;1701–1708) The savvy meat buyer in the Middle Ages was wary of buying a pig in a poke, or sack, for fear that what was actually concealed within the bag was something of lesser value. Similarly, scientists should be wary of somatic cell nuclear transfer (scNT) -derived animals, for they are not always quite what they seem. Previous reports demonstrated that there is phenotypic variability and abnormal gene expression among cloned animals, but a direct link between the two had been lacking. Here, Kim and colleagues connect the dots. Among eight scNT-derived pigs who were born with brown coat and skin color, one lost pigmentation after puberty. The affected pig not only lacked hair pigment and skin melanin granules, but also the melanocytes that produce them, and melanocyte precursors. The phenotype is reminiscent of Waardenburgh syndrome (WS), whose patients frequently harbor patches of depigmentation. mRNA levels of genes that cause WS, Sox10, pax3, and Mitf, and other pigmentation pathway genes, Slug and Kit, were tested and found to be severely decreased. DNA methylation patterns on the Kit promoter were also affected, including hypermethylated binding sites for the Sp1 transcription factor, which may block regulation of Kit expression. The findings suggest that scientists need not proceed blindly when using cloned animals if they can first ascertain the epigenetic and expression status of known genes of interest.
Dancing the two-step (Role of p21-activated Kinase in Cell Polarity and Directional Mesendoderm Migration in the Xenopus Gastrula by Martina Nagel, Olivia Luu, Nicolas Bisson, Bojan Macanovic, Tom Moss, and Rudolf Winklbauer, Dev Dyn238:1709–1726) During the complex dance that is Xenopus gastrulation, mesendoderm cells gracefully extend lamelliform protrusions that grasp the fibronectin (FN) -bearing extracellular matrix of the ectodermal blastocoel roof (BCR), propelling them toward the animal pole. Here, Winklbauer and colleagues explore the role of p21-activated kinase 1 (Pak1) in directed movement. While control mesodermal cells that have spread onto an FN-coated substrate have bipolar protrusions, those expressing a kinase-dead Pak1 (KD-Pak1) are stellate, with small protrusions around the cell's circumference. In contrast, cells expressing a constitutively active Pak1 (CA-Pak1) are initially bipolar, but have difficulty retracting lamellopodia, yielding a stellate morphology with long protrusions. These findings support the conclusion that Pak1 choreographs two steps, establishment (type I polarity) and maintenance (type II polarity), that lead to polarized protrusions. Are these polarization events required for directional migration? KD-Pak1 mesoderm explants plated onto a BCR conditioned substratum migrate in randomized directions rather than toward the animal pole. The phenotype is likely due to those cells sprouting nonpolarized protrusions, and being tightly packed. In a surprise performance, CA-Pak1 cells migrate normally, suggesting that type II polarity is unessential in this context. Another surprise, epistasis experiments place Pak1 upstream of Cdc42, Rac, and RhoA—an unexpected result because Paks are generally considered effectors of these Rho family GTPases. While performing the two-step, Pak1 pulls a one–two punch.