To proliferate or to die: role of Id3 in cell cycle progression and survival of neural crest progenitors

Abstract

The neural crest is a unique population of mitotically active, multipotent progenitors that arise at the vertebrate neural plate border. Here, we show that the helix-loop-helix transcriptional regulator Id3 has a novel role in cell cycle progression and survival of neural crest progenitors in Xenopus. Id3 is localized at the neural plate border during gastrulation and neurulation, overlapping the domain of neural crest induction. Morpholino oligonucleotide-mediated depletion of Id3 results in the absence of neural crest precursors and a resultant loss of neural crest derivatives. This appears to be mediated by cell cycle inhibition followed by cell death of the neural crest progenitor pool, rather than a cell fate switch. Conversely, overexpression of Id3 increases cell proliferation and results in expansion of the neural crest domain. Our data suggest that Id3 functions by a novel mechanism, independent of cell fate determination, to mediate the decision of neural crest precursors to proliferate or die.

Dissecting early regulatory relationships in the lamprey neural crest gene network

“…For example, it is clear that induction of Msx1 and Zic1/Pax3/7 represent independent events in the frog (3,4,22). Although classified as neural crest specifier genes, c-Myc, Id, and AP-2 are first deployed at the neural plate border of the early neurula, rather than in nascent neural crest cells (23)(24)(25)(26)(27)(28)(29). Because recent studies suggest that onset of neural crest formation and specifier expression in both frog and chick may occur in the gastrula, these genes may act earlier in neural crest specification than formerly assumed.…”

“…The second peak only becomes evident after E4. 25. The first peak in expression of MsxA, AP-2, ZicA, Id, and Pax3/7 most likely corresponds to different roles these genes play during gastrulation (i.e., prominent presence of MsxA activity in the lateral mesoderm, as shown by in situ analysis).…”

Id3 is a novel regulator of p27kip1 mRNA in early G1 phase and is required for cell-cycle progression

“…In addition, it has also been shown that E2A and Ids proteins participate to the transcriptional regulation of the cyclin-dependent kinase inhibitors (CKIs) p21 ink4a (Id1) (Zheng et al, 2004) in different biological models including senescence. Recent studies have shown that besides p21 and p16, Id1 and Id3 are also involved in the regulation of p27 protein, notably in Xenopus neural crest progenitors (Kee and Bronner-Fraser, 2005) and in Epstein-Barr virus infected cells (Everly et al, 2004); however, the molecular basis of this inhibition has never been elucidated.…”

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

“…Unlike Id-2 in chick which is merely involved in NC cell specification, Id-3 plays an essential role in their proliferation and survival as well as in the maintenance of a precursor pool of NC cells. 200,201 Coordination of transcriptional regulator activity during NC cell delamination. The above descriptive and functional studies indicate that NC cell delamination is achieved through cooperation of multiple transcriptional regulators in addition to members of the Snail, Zeb and bHLH families.…”