A morphogenetic wave in the chick embryo lateral mesoderm generates mesenchymal-epithelial transition through a 3D-rosette intermediate.

Formation of epithelia through mesenchymal-epithelial transition (MET) is essential for embryonic development and for many physiological and pathological processes. This study investigates MET in vivo in the chick embryo lateral mesoderm, where a multilayered mesenchyme transforms into two parallel epithelial sheets that constitute the coelomic lining of the embryonic body cavity. Prior to MET initiation, mesenchymal cells exhibit non-polarized distribution of multiple polarity markers, albeit not aPKC. We identified an epithelializing wave that sweeps across the lateral mesoderm, the wavefront of which is characterized by the accumulation of basal fibronectin and a network of 3D rosettes composed of polarized, wedge-shaped cells surrounding a central focus of apical markers, now including aPKC. Initiation of the MET process is dependent on extracellular matrix-integrin signaling acting through focal adhesion kinase and talin, whereas progression through the rosette phase requires aPKC function. We present a stepwise model for MET, comprising polarization, 3D-rosette, and epithelialization stages.

Regulation of aortic morphogenesis and VE-cadherin dynamics by VEGF.

In amniote vertebrates, the definitive dorsal aorta is formed by the fusion of two primordial aortic endothelial tubes. Formation of the definitive dorsal aorta requires extensive cellular migrations and rearrangements of the primordial tubes in order to generate a single vessel located at the embryonic ventral midline. This study examines the role of VEGF signaling in the generation of the definitive dorsal aorta. Through gain- and loss-of-function studies in vivo in the chick embryo, we document a requirement for VEGF signaling in growth and remodeling of the paired primordia. We find that regions of the aorta are differentially sensitive to levels of VEGF signaling, and present evidence that areas of low blood flow are more sensitive to the loss of VEGF signaling. We also find that VEGF signaling regulates the intracellular distribution between membrane and cytoplasm of the cell-cell adhesion molecule VE-cadherin in aortic endothelial cells in vivo. Together, these finding identify mechanisms that likely contribute to the dynamic behavior of endothelial cells during aorta morphogenesis.

Hedgehog Signaling Regulates Epithelial Morphogenesis to Position the Ventral Embryonic Midline.

Despite much progress toward understanding how epithelial morphogenesis is shaped by intra-epithelial processes including contractility, polarity, and adhesion, much less is known regarding how such cellular processes are coordinated by extra-epithelial signaling. During embryogenesis, the coelomic epithelia on the two sides of the chick embryo undergo symmetrical lengthening and thinning, converging medially to generate and position the dorsal mesentery (DM) in the embryonic midline. We find that Hedgehog signaling, acting through downstream effectors Sec5 (ExoC2), an exocyst complex component, and RhoU (Wrch-1), a small GTPase, regulates coelomic epithelium morphogenesis to guide DM midline positioning. These effects are accompanied by changes in epithelial cell-cell alignment and N-cadherin and laminin distribution, suggesting Hedgehog regulation of cell organization within the coelomic epithelium. These results indicate a role for Hedgehog signaling in regulating epithelial morphology and provide an example of how transcellular signaling can modulate specific cellular processes to shape tissue morphogenesis.