Ets-1 Confers Cranial Features on Neural Crest Delamination

Abstract

Neural crest cells (NCC) have the particularity to invade the environment where they differentiate after separation from the neuroepithelium. This process, called delamination, is strikingly different between cranial and trunk NCCs. If signalings controlling slow trunk delamination start being deciphered, mechanisms leading to massive and rapid cranial outflow are poorly documented. Here, we show that the chick cranial NCCs delamination is the result of two events: a substantial cell mobilization and an epithelium to mesenchyme transition (EMT). We demonstrate that ets-1, a transcription factor specifically expressed in cranial NCCs, is responsible for the former event by recruiting massively cranial premigratory NCCs independently of the S-phase of the cell cycle and by leading the gathered cells to straddle the basal lamina. However, it does not promote the EMT process alone but can cooperate with snail-2 (previously called slug) to this event. Altogether, these data lead us to propose that ets-1 plays a pivotal role in conferring specific cephalic characteristics on NCC delamination.

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

“…Similarly, ectopic expression of the Ets1 transcription factor induces NE cell delamination independently of a NC phenotype but fails to promote migration. Expressing both Snail2 and Ets1 confers full capacity to migrate (Théveneau et al, 2007), and knocking down Snail2 does not alter NC delamination but results in apoptosis during migration (Cheung et al, 2005;Teng et al, 2008). These observations indicate that NE cell ability to delaminate is not sufficient for adopting NC features and that, conversely, acquisition of NC identity is not necessary for delamination but is a prerequisite for survival.…”

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

“…to provoke EMT of neural epithelial cells (del Barrio and Nieto, 2002;Cheung et al, 2005;Theveneau et al, 2007). All together, these observations suggest possible antagonistic roles for Snail-2 and Zeb-2 in the control of EMT in neurectodermal cells, irrespective of their function as cadherin regulators.…”

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

“…In summary, cranial NC cell delamination occurs all at once and massively in a discrete portion of the neural epithelium, immediately after its invagination, all features characteristic of en masse EMT. [54][55][56] In contrast to the head, the onset of NC cell delamination in the trunk is clearly uncoupled from closure of the neural tube, indicating that, in this region, the determinism of the triggering of EMT does not reside in the fold fusion (Fig. 4B).…”

“…In striking contrast with the massive and rapid emergence of cranial NC cells, truncal NC cells emigrate individually from the dorsal neural tube, in a dripping fashion over a long period of time extending beyond 40 h. [59][60][61][62] This very gradual segregation of NC cells in the trunk stems primarily from the fact that in this region, EMT is coupled to the cell cycle. 55,63 In the avian embryo, NC cells synchronously emigrate from the neural tube in the S-phase, when the nucleus is closest to the basal side, and specific inhibition of the G 1 /S transition provokes severe reduction in delamination, without affecting specification. 63 Moreover, recent studies have shown that NC cell progenitors are initially distributed in a broad region in the dorsal region of the neural tube and that they become gradually confined to a narrow band at the apex of the tube as delamination progresses.…”

“…108 Consistent with this, the transcriptional regulator Ets-1 known to induce expression of MMPs is upregulated in cranial NC cells in the chick and frog, precisely at the time of NC cell delamination, and overexpression of Ets-1 in the neural tube causes ectopic delamination of neural epithelial cells associated with degradation of the basal lamina. 55,109 Other studies showed that a subset of NC cells in the hindbrain at the origin of the cardiac NC do not produce MMP-2 by themselves but use for migration MMP-2 released in their environment by mesodermal cells. 110,111 As mentionned before, NC cells also synthesize ADAM proteases such as ADAM-10 in the chick 91 and ADAM-13 in the frog.…”