Developmental Dynamics

Key findings:

• Rab11 is enriched and polarized in multiciliated skin cells and their precursors.

• Interference with Rab11 function in ciliated cell precursors causes migration defects and formation of randomly oriented apical domains.

• Rab11 is required for the initial polarization of ciliated cell precursors, which is necessary for their intercalation into the superficial ectodermal layer.

Key Findings:

• The stapedial footplate is of neural crest and mesoderm origin.

• The otic capsule contributes to the stapedial footplate.

• The neural crest component of the stapedial footplate is needed for development of the mesodermal component and for proper formation of the oval window.

• The position of the oval window appears independent of the stapes.

Key Findings:

• Gbx1 is involved in feather-bud formation.

• Retinoic acid inhibits feather-bud formation, induces transdifferentiation of epidermis to mucosal epithelium, and increases Gbx1 expression.

• Transfection of the epidermis with Gbx1 cDNA induces elongation of the feather bud, but does not induce transdifferentiation.

Key findings:

• The addition of Nkx2.5-positive myocardial precursors from the anterior heart field occurs during normal development in an asymmetrical fashion, predominantly below the left branch of the 6th pharyngeal arch artery.

• The continued addition of right-sided myocardium during normal development results in movement without spiralization of the OFT in which the pulmonary trunk orifice is pushed in a rightward and anterior direction, a mechanism referred to as “pulmonary push.”

• Deficient or disorganized positioning of the Nkx2.5-positive precursors, as was observed in VEGF120/120 mutants might explain cardiac malformations with side-by-side position of the great arteries, such as double outlet right ventricle.

Key findings:

• We present a technique to double-label endothelial cells and macrophages with PKH26-PCL and AcLDL for in vivo time-lapsing.

• The majority of double-labeled cells displayed an endothelial-like morphology, incorporating in the vessel wall and expressing Tie1, suggesting a myeloid-origin to some cells in the vessel wall.

• Double-labeled cells that had integrated in the wall were largely immobile during normal development, however, could be recruited when remodeling was induced in the vascular network.

Key findings:

• A genome-scale in situ hybridization screen for transcription factor gene expression in the pseudoglandular stage embryonic mouse lung.

• Sixty-two transcription factor genes were highlighted to be expressed in distinct sub-regions of the lung epithelium and/or mesenchyme.

• A number of the identified genes are not previously implicated in lung development.

Key findings:

• ETV2 expression is tightly associated with the onset of yolk sac hematopoiesis.

• In vitro and in vivo, ETV2 is expressed not only in FLK1⁺ cells but also in the TIE2⁺cKIT⁺ hemogenic endothelium.

• ETV2 is absolutely required for the formation of the hemogenic endothelium.

Key findings:

• Extra incisor tooth formation was found in ShhCre/Dicer^fl/fl mice.

• Wnt1Cre/Dicer^fl/fl mice showed an arrest or absence of teeth development, which varied in frequency between incisors and molars.

• Microarray an in situ hybridization analysis identified several miRNAs that showed differential expression between incisors and molars.

Key findings:

• The majority of scattered Lyve-1⁺ cells invading the embryonic heart possess the CD68 or the CD45 marker but not the CD31. A few scattered Lyve-1⁺ cells exhibit the CD11b or F4/80 antigen but not the CD31.

• Lyve-1⁺/CD45⁺, Lyve-1⁺/CD68, Lyve-1⁺/CD11b⁺, and Lyve-1⁺/F4/80⁺ cells can be found in the lymphatic vessel wall (Lyve-1⁺/Prox-1⁺) once they have gained the Flk-1 antigen.

• Apart from entering the embryonic heart via the arterial pole, the lymphatics invade also the venous pole, i.e., atrioventricular sulcus of the dorsal aspect of the heart and the dorsal aspect of the atrial surface.

• The cellular phenotypes and spatio-temporal pattern of lymphatic primordia differ at the venous pole in comparison with the arterial pole.

Key findings:

• A microarray assay and secondary confirmation of Pitx3 morphants indicates that Pax6, β Crystallin-b1 (Crybb1), Hes7.1, and Hes4 are good candidates for direct targets.

• Four other genes show equivocal promise worthy of consideration: Vent2, and Ripply2 (aka Ledgerline or Stripy), eFGF and RXRα.

• Novel genes described (but that are likely indirectly affected) are described: Rbp4l, Galectin IX, Baz2b, and Rdh16.

• In addition to previously described interactions in lens and brain, Pitx3 also intersects the segmentation pathway and retinoid regulation.