Cell delamination in the mesencephalic neural fold and its implication for the origin of ectomesenchyme

Abstract

The neural crest is a transient structure unique to vertebrate embryos that gives rise to multiple lineages along the rostrocaudal axis. In cranial regions, neural crest cells are thought to differentiate into chondrocytes, osteocytes, pericytes and stromal cells, which are collectively termed ectomesenchyme derivatives, as well as pigment and neuronal derivatives. There is still no consensus as to whether the neural crest can be classified as a homogenous multipotent population of cells. This unresolved controversy has important implications for the formation of ectomesenchyme and for confirmation of whether the neural fold is compartmentalized into distinct domains, each with a different repertoire of derivatives. Here we report in mouse and chicken that cells in the neural fold delaminate over an extended period from different regions of the cranial neural fold to give rise to cells with distinct fates. Importantly, cells that give rise to ectomesenchyme undergo epithelial-mesenchymal transition from a lateral neural fold domain that does not express definitive neural markers, such as Sox1 and N-cadherin. Additionally, the inference that cells originating from the cranial neural ectoderm have a common origin and cell fate with trunk neural crest cells prompted us to revisit the issue of what defines the neural crest and the origin of the ectomesenchyme.

Cadherin 6 promotes neural crest cell detachment via F-actin regulation and influences active Rho distribution during epithelial-to-mesenchymal transition

“…Collectively, these studies suggest diverse molecular functions for Cdh6 that may differ between trunk and cranial NCCs, and also between subpopulations of cranial NCCs (midbrain versus hindbrain). Interestingly, distinct pre-migratory cell populations within the cranial neural fold give rise to different NCC derivatives (Lee et al, 2013), and differences in cadherin expression may define subpopulations. At different stages of NCC EMT, we see little or no cdh6 expression in the zebrafish midbrain and low levels in the hindbrain, which could indicate different roles for Cdh6 in these areas.…”

Cadherins function during the collective cell migration of Xenopus Cranial Neural Crest cells: revisiting the role of E-cadherin

“…The change of expression in cadherins, called cadherin switch, is pivotal in both instances (Duband et al, 1988; Nieto et al, 2016). However, in the CNC, which are not part of the closing neural tube, persistent expression of E-cadherin has been observed in pre-migratory and early migratory stages (Dady et al, 2012; Lee et al, 2013). While these observations need to be further explored in other species, they suggest that the CNC, at least in two animal species, may have slightly different mechanism to achieve their migration.…”

Resolving Time and Space Constraints During Neural Crest Formation and Delamination

“…studies argue that N-cadherin may not be implicated at all or at least very secondarily in NCC delamination in the rostral half of the embryo. A detailed description of the kinetics of NCC delamination at the midbrain level in chick and mouse (Lee et al, 2013) revealed that a large proportion of the delaminating cells do not express N-cadherin but rather E-cadherin, which is gradually repressed as they separate from the neurectoderm. Interestingly, these cells are located adjacent to the nonneural ectoderm in the neural folds and correspond to the mesectodermal contingent of cranial NCC (i.e., cells at the origin of bones, cartilage, and other nonneural derivatives).…”

“…As discussed earlier, this role is most likely devoted to cadherin-6B whose repression occurs sharply. The function of E-cadherin in this process is apparently less critical as its repression proceeds at a slow pace and that, depending on the axial level considered, it may be expressed on the surface of migrating cells (though at moderate levels) or downregulated prior to delamination (Dady et al, 2012;Dady & Duband, 2015;Lee et al, 2013). This view is consistent with the expression patterns and functions during delamination of Snail-2 and Zeb-2, known as bona fide transcriptional repressors of E-cadherin and cadherin-6B (Peinado et al, 2007;Taneyhill et al, 2007) but not of N-cadherin (Dady et al, 2012;Dady & Duband, 2015).…”