The neural crest epithelial-mesenchymal transition in 4D: a `tail' of multiple non-obligatory cellular mechanisms

Abstract

An epithelial-mesenchymal transition (EMT) is the process whereby epithelial cells become mesenchymal cells, and is typified by the generation of neural crest cells from the neuroepithelium of the dorsal neural tube. To investigate the neural crest EMT, we performed live cell confocal time-lapse imaging to determine the sequence of cellular events and the role of cell division in the EMT. It was observed that in most EMTs, the apical cell tail is retracted cleanly from the lumen of the neuroepithelium, followed by movement of the cell body out of the neural tube. However, exceptions to this sequence include the rupture of the neural crest cell tail during retraction (junctional complexes not completely downregulated), or translocation of the cell body away from the apical surface while morphologically rounded up in M phase (no cell tail retraction event). We also noted that cell tail retraction can occur either before or after the redistribution of apical-basolateral epithelial polarity markers. Surprisingly, we discovered that when an EMT was preceded by a mitotic event, the plane of cytokinesis does not predict neural crest cell fate. Moreover, when daughter cells are separated from the adherens junctions by a parallel mitotic cleavage furrow, most re-establish contact with the apical surface. The diversity of cellular mechanisms by which neural crest cells can separate from the neural tube suggests that the EMT program is a complex network of non-linear mechanisms that can occur in multiple orders and combinations to allow neural crest cells to escape from the neuroepithelium.

Rho activation is apically restricted by Arhgap1 in neural crest cells and drives epithelial-to-mesenchymal transition

“…1A). One of the first discernible behaviors of NCC EMT is the detachment of the cell 'tail' from the apical midline, which is preceded by or coincides with loss of apical cell junction components (Ahlstrom and Erickson, 2009). After detachment the trailing tail continues to retract as the cell rounds at the basal side of the neuroepithelium where it begins membrane blebbing and subsequently delaminates (Berndt et al, 2008).…”

Controlled levels of canonical Wnt signaling are required for neural crest migration

“…NC cells are subdivided into cranial (Graham et al, 2004;Cordero et al, 2011), cardiac (Kirby et al, 1983;Keyte and Hutson, 2012), vagal (Kuo and Erickson, 2011;Peters-Van Der Sanden et al, 1993;Burns and Le Douarin, 1998;Yntema and Hammond, 1954), trunk (Bronner-Fraser and Fraser, 1989;Serbedzija et al, 1994) and sacral (Burns and Le Douarin, 1998;Anderson et al, 2006) NC cells due to their diversity along neuraxis ( Fig.1.1A). Upon closure of the neural plate, NC cells undergo epithelial-to-mesenchymal transition (EMT) (Ahlstrom and Erickson, 2009;Alfandari et al, 2010;Berndt et al, 2008 andDuband, 2010) allowing them to delaminate from prospective neural tube and migrate throughout the embryo ( Fig.1.1B). Many of the genes involved in EMT of NC cells are transcription factors which have been also classified as proto-oncogenes contributing to cancer development (Thiery, 2003).…”

“…The core of EMT is the breakdown of the highly integrated epithelium and formation of the mesenchymal cells causing complex tissue rearrangements common in early embryogenesis and tumor metastasis ( Fig.1.5) (Nieto, 2011;Thiery et al, 2009). During EMT cells can go through the series of transient stages, from typical epithelial tissues with firm cell-cell adhesions, to not fully determined mesenchymal cells with transient contacts and finally to the entirely separated mesenchymal cell without epithelial polarity and cell-cell adhesions Ahlstrom and Erickson, 2009;Baum et al, 2008;Duband, 2010;Theveneau and Mayor, 2012 (Vallin et al, 2001;Yook et al, 2006;Thiery and Sleeman, 2006) and numerous transcription factors belonging to the group of NC-specifires.…”

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

“…55 Moreover, truncal NC cells can be forced to undergo EMT in a non-coordinated manner with the cell cycle when overexpressing Ets-1, 55 suggesting that that EMT may to some extent be uncoupled from the cell cyle (reviewed in ref. 213). As discussed above, it is rather the conjunction between the presence of the nucleus at the basal side with the disruption of the basal lamina that favors EMT.…”

“…213 This study performed at the trunk level of chick embryos allowed to visualize directly the dynamics of NC cell EMT and solved several issues regarding the cellular mechanism of the EMT, such as the sequence of events, modes of detachment and the role of cell division in generating NC cells. A major conclusion is that NC cells can separate from the neural tube by a great diversity of cellular mechanisms, thereby revealing that their EMT program is governed by a complex network of non-linear, independent and loosely-connected mechanisms that can occur in multiple orders and combinations to allow NC cells to escape from the neural epithelium.…”