Early stages of neural crest ontogeny: formation and regulation of cell delamination

Abstract

Long standing research of the Neural Crest embodies the most fundamental questions of Developmental Biology. Understanding the mechanisms responsible for specification, delamination, migration and phenotypic differentiation of this highly diversifying group of progenitors has been a challenge for many researchers over the years and continues to attract newcomers into the field. Only a few leaps were more significant than the discovery and successful exploitation of the quail-chick model by Nicole Le Douarin and colleagues from the Institute of Embryology at Nogent-sur-Marne. The accurate fate mapping of the neural crest performed at virtually all axial levels was followed by the determination of its developmental potentialities as initially analysed at a population level and then followed by many other significant findings. Altogether, these results paved the way to innumerable questions which brought us from an organismic view to mechanistic approaches. Among them, elucidation of functions played by identified genes is now rapidly underway. Emerging results lead the way back to an integrated understanding of the nature of interactions between the developing neural crest and neighbouring structures. The Nogent Institute thus performed an authentic «tour de force» in bringing the Neural Crest to the forefront of Developmental Biology. The present review is dedicated to the pivotal contributions of Nicole Le Douarin and her collaborators and to unforgettable memories that one of the authors bears from the time spent in the Nogent Institute. We summarize here recent advances in our understanding of early stages of crest ontogeny that comprise specification of epithelial progenitors to a neural crest fate and the onset of neural crest migration. Particular emphasis is given to signaling by BMP and Wnt molecules, to the role of the cell cycle in generating cell movement and to possible interactions between both mechanisms.

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“…The EMT involves different molecular and cellular machineries and implies deep changes in cell morphology and in the type of cell surface adhesion and recognition molecules. After completing EMT, the NCC delaminate from the epithelial neural folds/neural tube and start migrating along characteristic pathways to differentiate into a wide variety of derivatives [2].…”

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

“…An integrated control has only been provided for NC cells in which the activities of Wnt1, BMP4, and its antagonist Noggin have been found to orchestrate NC cell adhesion, proliferation, and specification during delamination (Kalcheim and Burstyn-Cohen, 2005;Duband, 2006). Conversely, in vitro, SHH has been shown to alter NE and NC cell adhesion properties, causing repression of NC cell delamination (Testaz et al, 2001), but the importance of this effect in neural tube morphogenesis has not been investigated.…”

Dynamic Alterations in Gene Expression after Wnt-mediated Induction of Avian Neural Crest

“…In particular, the BMP signaling pathway has been reported to be involved in the processes of neural crest induction and delamination (for review see Knecht and Bronner-Fraser, 2002;Huang and Saint-Jeannet, 2004;Kalcheim and Burstyn-Cohen, 2005). Inhibition of BMP signaling by the secreted molecules chordin, noggin and follistatin is necessary for neural differentiation in Xenopus.…”