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Development. May 1, 2005; 132 (10): 2401-13.

Six3 functions in anterior neural plate specification by promoting cell proliferation and inhibiting Bmp4 expression.

Gestri G , Carl M , Appolloni I , Wilson SW , Barsacchi G , Andreazzoli M .

Although it is well established that Six3 is a crucial regulator of vertebrate eye and forebrain development, it is unknown whether this homeodomain protein has a role in the initial specification of the anterior neural plate. In this study, we show that exogenous Six3 can expand the anterior neural plate in both Xenopus and zebrafish, and that this occurs in part through Six3-dependent transcriptional regulation of the cell cycle regulators cyclinD1 and p27Xic1, as well as the anti-neurogenic genes Zic2 and Xhairy2. However, Six3 can still expand the neural plate in the presence of cell cycle inhibitors and we show that this is likely to be due to its ability to repress the expression of Bmp4 in ectoderm adjacent to the anterior neural plate. Furthermore, exogenous Six3 is able to restore the size of the anterior neural plate in chordino mutant zebrafish, indicating that it has the ability to promote anterior neural development by antagonising the activity of the BMP pathway. On its own, Six3 is unable to induce neural tissue in animal caps, but it can do so in combination with Otx2. These results suggest a very early role for Six3 in specification of the anterior neural plate, through the regulation of cell proliferation and the inhibition of BMP signalling.

PubMed ID: 15843413
PMC ID: PMC2789257
Article link: Development.
Grant support: 074376 Wellcome Trust , GGP04268 Telethon, TI_GGP04268 Telethon, WT074376 Wellcome Trust

Genes referenced: ascl2 bmp4 cdknx chrd.1 dhh elavl1 elavl3 foxg1 hes4 neurog1 neurog2 nppa otx2 pnp rax shh six3 sox2 tubb2b xk81a1 zic2

Morpholinos referenced: six3 MO1 six3 MO2 six3 MO3

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