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Dev Biol October 15, 2008; 322 (2): 355-67.

Hairy2-Id3 interactions play an essential role in Xenopus neural crest progenitor specification.

Nichane M , de Crozé N , Ren X , Souopgui J , Monsoro-Burq AH , Bellefroid EJ .

Loss of function studies have shown that the Xenopus helix-loop-helix transcription factor Hairy2 is essential for neural crest formation and maintains cells in a mitotic undifferentiated state. However, its position in the genetic cascade regulating neural crest formation and its relationship with other neural crest regulators remain largely unknown. Here we find that Hairy2 is regulated by BMP, FGF and Wnt and that it is only required downstream of BMP and FGF for neural crest formation. We show that Hairy2 overexpression represses neural crest and upregulates neural border genes at early stages while it expands a subset of them in later embryos. We show that Hairy2 downregulates Id3, another essential HLH neural crest regulator, through attenuation of BMP signaling. Knockdown and rescue experiments indicate that Id3 protein, which physically interacts with Hairy2, negatively regulates Hairy2 activity. However, Id3 is required to allow Hairy2 to promote neural crest formation. Together, our results provide evidence that Hairy2 acts downstream of FGF and BMP signals at the neural border to maintain cells in an undifferentiated state, and that Hairy2-Id3 interactions play an essential role in neural crest progenitor specification.

PubMed ID: 18721802
Article link: Dev Biol

Genes referenced: ag1 ank1 ankh bmp4 bmpr1a dct fgf8 fgfr4 foxd3 hes1 hes2 hes4 hes6.2 hoxb9 hoxc9-like id3 krt12.4 msx1 myc myod1 myt1 neurod1 nog notch1 nrp1 otx2 pax3 pax8 ranbp2 six1 six3 snai2 sox10 sox15 sox2 sox3 sox9 st14 tbxt trpc2 tubb2b wnt7b wnt8a zic1
Morpholinos: fgf8 MO1 hes4 MO1 hes4 MO2 id3 MO2 msx1 MO3 pax3 MO4 zic1 MO1

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