Cadherin-6B is rapidly depleted from premigratory neural crest cells during EMT, suggestive of posttranslational mechanisms. ADAM10, ADAM19, and γ-secretase cleave cadherin-6B, and ADAM perturbation alters the premigratory neural crest cell domain. The study provides the first evidence for cadherin-6B proteolysis in neural crest cells during EMT.

The neural crest is a transient population of migratory cells that differentiates to form a variety of cell types in the vertebrate embryo, including melanocytes, the craniofacial skeleton, and portions of the peripheral nervous system. These cells initially exist as adherent epithelial cells in the dorsal aspect of the neural tube and only later become migratory after an epithelial-to-mesenchymal transition (EMT). Snail2 plays a critical role in mediating chick neural crest cell EMT and migration due to its expression by both premigratory and migratory cranial neural crest cells and its ability to down-regulate intercellular junctions components. In an attempt to delineate the role of cellular junction components in the neural crest, we have identified the adherens junction molecule neural alpha-catenin (αN-catenin) as a Snail2 target gene whose repression is critical for chick neural crest cell migration. Knock-down and overexpression of αN-catenin enhances and inhibits neural crest cell migration, respectively. Furthermore, our results reveal that αN-catenin regulates the appropriate movement of neural crest cells away from the neural tube into the embryo. Collectively, our data point to a novel function of an adherens junction protein in facilitating the proper migration of neural crest cells during the development of the vertebrate embryo.

Neural crest cells give rise to a diverse range of structures during vertebrate development. These cells initially exist in the dorsal neuroepithelium and subsequently acquire the capacity to migrate. Although studies have documented the importance of adherens junctions in regulating neural crest cell migration, little attention has been paid to tight junctions during this process. We now identify the tight junction protein cingulin as a key regulator of neural crest migration. Cingulin knock-down increases the migratory neural crest cell domain, which is correlated with a disruption of the neural tube basal lamina. Overexpression of cingulin also augments neural crest cell migration and is associated with similar basal lamina changes and an expansion of the premigratory neural crest population. Cingulin overexpression causes aberrant ventrolateral neuroepithelial cell delamination, which is linked to laminin loss and a decrease in RhoA. Together, our results highlight a novel function for cingulin in the neural crest.

The neural crest is a population of migratory cells that follows specific pathways during development, eventually differentiating to form parts of the face, heart, and peripheral nervous system, the latter of which includes contributions from placodal cells derived from the ectoderm. Stationary, premigratory neural crest cells acquire the capacity to migrate by undergoing an epithelial-to-mesenchymal transition that facilitates their emigration from the dorsal neural tube. This emigration involves, in part, the dismantling of cell-cell junctions, including apically localized tight junctions in the neuroepithelium. In this study, we have characterized the role of the transmembrane tight junction protein claudin-1 during neural crest and placode ontogeny. Our data indicate that claudin-1 is highly expressed in the developing neuroepithelium but is down-regulated in migratory neural crest cells, although expression persists in the ectoderm from which the placode cells arise. Depletion or overexpression of claudin-1 augments or reduces neural crest cell emigration, respectively, but does not impact the development of several cranial placodes. Taken together, our results reveal a novel function for a tight junction protein in the formation of migratory cranial neural crest cells in the developing vertebrate embryo.

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Neural crest cells are a transient, multi-potent cell population requisite for vertebrate development. Premigratory neural crest cells exist as adherent epithelial cells and undergo an epithelial-tomesenchymal transition (EMT) to become motile. After cessation of migration, these cells differentiate to form parts of the peripheral nervous system, melanocytes, and the craniofacial skeleton. At the onset of EMT, premigratory neural crest cells lose intercellular contacts mediated by both adherens junctions and tight junctions in order to facilitate emigration of cells out of the dorsal neural tube. We now show that cingulin, a tight junction scaffolding protein, plays an important role in controlling chick midbrain neural crest cell delamination and migration. Overexpression of cingulin enhances emigration of neural crest cells and leads to ectopic delamination of more ventrolateral neuroepithelial cells. Cingulin depletion also augments neural crest cell emigration through the premature and persistent loss of laminin and Cad6B. Our data indicate that cingulin may carry out this function through effects on Rho proteins. Taken together, our results show that cingulin plays a crucial function in the development of the vertebrate embryo through the modulation of neural crest and neuroepithelial cell delamination.The neural crest is a population of migratory cells that follows specific pathways during development, eventually differentiating to form parts of the face, heart, and peripheral nervous system. Stationary, premigratory neural crest cells (NCCs) in the dorsal neural tube transition to migratory NCCs through the loss of cellcell junctions, including tight junctions, during the NCC epithelialto-mesenchymal transiton (EMT). Tight junctions (TJs) are located on the apical side of epithelial cells and serve to maintain cell polarity and to form a barrier that prevents the flow of molecules between the apical and basolateral surfaces of cells. Our data suggest that the TJ transmembrane molecule claudin-1 is a candidate protein that may play a role in NCC development. We have characterized the RNA and protein distribution of claudin-1 at various stages of chick embryonic development, focusing on the midbrain region prior to and after NCC migration. Our results indicate that claudin-1 mRNA is localized to premigratory NCCs in the dorsal neural folds before NCC EMT, and claudin-1 protein is distributed along the apical region of the neural tube. Importantly, claudin-1 transcripts and protein are not observed in migratory NCCs. We will next investigate the effects of claudin-1 depletion and overexpression on NCC EMT and migration. Our experiments will reveal the functional role of claudin-1, and the importance of dismantling TJs in the proper migration of NCCs to build the vertebrate embryo.The development of the lower jaw is regulated spatiotemporally by signaling cascades, and is refined through both permissive and inhibitory signals. We have shown that endothelin-A receptor (Ednra) signaling is a central regulator of...