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XB-ART-39749
Dev Biol May 1, 2009; 329 (1): 80-95.

foxD5 plays a critical upstream role in regulating neural ectodermal fate and the onset of neural differentiation.



Abstract
foxD5 is expressed in the nascent neural ectoderm concomitant with several other neural-fate specifying transcription factors. We used loss-of-function and gain-of-function approaches to analyze the functional position of foxD5 amongst these other factors. Loss of FoxD5 reduces the expression of sox2, sox11, soxD, zic1, zic3 and Xiro1-3 at the onset of gastrulation, and of geminin, sox3 and zic2, which are maternally expressed, by late gastrulation. At neural plate stages most of these genes remain reduced, but the domains of zic1 and zic3 are expanded. Increased FoxD5 induces geminin and zic2, weakly represses sox11 at early gastrula but later (st12) induces it; weakly represses sox2 and sox3 transiently and strongly represses soxD, zic1, zic3 and Xiro1-3. The foxD5 effects on zic1, zic3 and Xiro1-3 involve transcriptional repression, whereas those on geminin and zic2 involve transcriptional activation. foxD5''s effects on geminin, sox11 and zic2 occur at the onset of gastrulation, whereas the other genes require earlier foxD5 activity. geminin, sox11 and zic2, each of which is up-regulated directly by foxD5, are all required to account for foxD5 phenotypes, indicating that this triad constitutes a transcriptional network rather than linear path that coordinately up-regulates genes that promote an immature neural fate and inhibits genes that promote the onset of neural differentiation. We also show that foxD5 promotes an ectopic neural fate in the epidermis by reducing BMP signaling. Several of the genes that are repressed by foxD5 in turn reduce foxD5 expression, contributing to the medial-lateral patterning of the neural plate.

PubMed ID: 19250931
PMC ID: PMC2672197
Article link: Dev Biol
Grant support: [+]
Genes referenced: acss2.2 foxd4l1.1 gal.2 gem gmnn irx1 irx2 irx3 klf6 krt12.4 myc sox11 sox15 sox2 sox3 st13 st14 szl tfap2a zic1 zic2 zic3
Antibodies: Smad1 Ab7
Morpholinos: foxd4l1.1 MO1 foxd4l1.2 MO1


Article Images: [+] show captions
References [+] :
Aruga, Zic1 promotes the expansion of dorsal neural progenitors in spinal cord by inhibiting neuronal differentiation. 2002, Pubmed


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