Background: During embryonic development, cadherin switches are correlated with tissue remodelings, such as epithelium-to-mesenchyme transition (EMT). An E-to N-cadherin switch also occurs during neurogenesis, but this is not accompanied with EMT. The biological significance of this switch is currently unknown. Results: We analyzed the timing and kinetics of the E-to N-cadherin switch during early neural induction and neurulation in the chick embryo, in relation to the patterns of their transcriptional regulators. We found that deployment of the E-to N-cadherin switch program varies considerably along the embryonic axis. Rostrally in regions of primary neurulation, it occurs progressively both in time and space in a manner that appears neither in connection with morphological transformation of neural epithelial cells nor in synchrony with movements of neurulation. Caudally, in regions of secondary neurulation, neurogenesis was not associated with cadherin switch as N-cadherin pre-existed before formation of the neural tube. We also found that, during neural development, cadherin switch is orchestrated by a set of transcriptional regulators distinct from those involved in EMT. Conclusions: Our results indicate that cadherin switch correlates with the partition of the neurectoderm into its three main populations: ectoderm, neural crest, and neural tube.

Rationale: Cardiac neural crest cells (NCs) contribute to heart morphogenesis by giving rise to a variety of cell types from mesenchyme of the outflow tract, ventricular septum, and semilunar valves to neurons of the cardiac ganglia and smooth muscles of the great arteries. Failure in cardiac NC development results in outflow and ventricular septation defects commonly observed in congenital heart diseases. Cardiac NCs derive from the vagal neural tube, which also gives rise to enteric NCs that colonize the gut; however, so far, molecular mechanisms segregating these 2 populations and driving cardiac NC migration toward the heart have remained elusive. Objective: Stromal-derived factor-1 (SDF1) is a chemokine that mediates oriented migration of multiple embryonic cells and mice deficient for Sdf1 or its receptors, Cxcr4 and Cxcr7 , exhibit ventricular septum defects, raising the possibility that SDF1 might selectively drive cardiac NC migration toward the heart via a chemotactic mechanism. Methods and Results : We show in the chick embryo that Sdf1 expression is tightly coordinated with the progression of cardiac NCs expressing Cxcr4 . Cxcr4 loss-of-function causes delayed migration and enhanced death of cardiac NCs, whereas Sdf1 misexpression results in their diversion from their normal pathway, indicating that SDF1 acts as a chemoattractant for cardiac NCs. These alterations of SDF1 signaling result in severe cardiovascular defects. Conclusions: These data identify Sdf1 and its receptor Cxcr4 as candidate genes responsible for cardiac congenital pathologies in human.