N-cadherinis required for the polarized cell behaviors that drive neurulation in the zebrafish

Abstract

Through the direct analysis of cell behaviors, we address the mechanisms underlying anterior neural tube morphogenesis in the zebrafish and the role of the cell adhesion molecule N-cadherin (N-cad) in this process. We demonstrate that although the mode of neurulation differs at the morphological level between amphibians and teleosts, the underlying cellular mechanisms are conserved. Contrary to previous reports, the zebrafish neural plate is a multi-layered structure, composed of deep and superficial cells that converge medially while undergoing radial intercalation, to form a single cell-layered neural tube. Time-lapse recording of individual cell behaviors reveals that cells are polarized along the mediolateral axis and exhibit protrusive activity. In N-cad mutants, both convergence and intercalation are blocked. Moreover, although N-cad-depleted cells are not defective in their ability to form protrusions, they are unable to maintain them stably. Taken together, these studies uncover key cellular mechanisms underlying neural tube morphogenesis in teleosts, and reveal a role for cadherins in promoting the polarized cell behaviors that underlie cellular rearrangements and shape the vertebrate embryo.

Sonic Hedgehog Regulates Integrin Activity, Cadherin Contacts, and Cell Polarity to Orchestrate Neural Tube Morphogenesis

“…The local restriction of SHH effect on cell adhesion matches the time when the neural epithelium acquires its pseudostratified aspect (Hong and Brewster, 2006;Duband et al, 2009). Caudal NE cells are poorly cohesive, not fully polarized, and spread onto matrices using their activated ␤1 integrins, which are uniformly distributed on their surface.…”

Timing and kinetics of E‐ to N‐cadherin switch during neurulation in the avian embryo

“…These observations fully support previous genetic studies in the mouse and Zebrafish showing that, in the absence of N-cadherin, onset of formation of the neural epithelium develops normally. The first signs of neural tube malformations are detected relatively late, in the mouse, by the appearance of undulations along the neural tube after closure (Radice et al, 1997) and, in the fish, by the absence of cavitation due to alterations in movements of convergence and intercalation (Hong and Brewster, 2006). Therefore, rather than a prerequisite to the morphological changes, cadherin switch appears merely as a secondary event during neurulation.…”

“…This E-to Ncadherin switch during neurulation has often been interpreted as an event necessary both for the acquisition of the morphological features of neural epithelial cells and for the movements of neurulation to occur. However, despite a variety of experiments in different animal models that uncovered the importance of N-cadherin in early neural development (Bronner-Fraser et al, 1992;Radice et al, 1997;Lele et al, 2002;Hong and Brewster, 2006;Nandadasa et al, 2009), these hypotheses have never been tested experimentally, and the biological significance of the change in cadherin expression during neurulation remains, therefore, unclear. In particular, it is not known why, contrary to epithelial cell lines established in vitro, E-cadherin loss in the neural epithelium does not provoke EMT.…”

Diversity in the molecular and cellular strategies of epithelium-to-mesenchyme transitions: Insights from the neural crest

“…Secondary neurulation, in contrast, proceeds through an almost converse process, related to some extent to mesenchyme-to-epithelium transition, while in zebrafish, it involves mostly the transition between an immature epitheliallike multilayered tissue composed of poorly organized cells into a more stable pseudo-stratified epithelium with fully polarized cells. 45 Thus, depending on their origin, the natural history of neural epithelial cells varies considerably, and it is therefore likely that such a diversity will be reflected by the cellular and molecular events accompanying NC cell EMT and/or by their kinetics. However, so far, this question remains elusive as it is only relatively recently that the fate map of NC cell progenitors has been established for the anterior regions of the embryo.…”

“…3C). 40,45 The neural plate starts out as a multilayered tissue, composed of deep and superficial cells. Deep cells have a columnar, epithelial-like morphology and are anchored to a basement membrane whereas superficial cells are more cuboidal in shape.…”