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Development 2005 Jul 01;13214:3267-79. doi: 10.1242/dev.01905.
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Cooperative requirement of the Gli proteins in neurogenesis.

Nguyen V , Chokas AL , Stecca B , Ruiz i Altaba A .

The Gli proteins are critical components of multiple processes in development, homeostasis and disease, including neurogenesis and tumorigenesis. However, it is unclear how the Gli code, the sum of their combinatorial positive and negative functions, dictates cell fate and behavior. Using an antisense approach to knockdown gene function in vivo, we find that each of the three Gli proteins is required for the induction of all primary neurons in the amphibian neural plate and regulates the bHLH/Notch neurogenic cascade. Analyses of endogenous Gli function in Gli-mediated neurogenesis and tumorigenesis, and in animal cap assays, reveal specific requirements that are context specific. Nuclear colocalization and binding studies suggest the formation of complexes, with the first two zinc fingers of the Gli five zinc-finger domain acting as a protein-protein interaction site. The Gli proteins therefore appear to form a dynamic physical network that underlies cooperative function, greatly extending the combinatorial possibilities of the Gli code, which may be further fine-tuned in cell fate specification by co-factor function.

PubMed ID: 15983404
PMC ID: PMC1405824
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: ascl2 foxa4 gal.2 gli1 gli2 gli3 myc myt1 neurod1 neurog1 runx1 shh snai1 snai2 sox3 tbx2 tubb2b zic2
Antibodies: Myc Ab6
Morpholinos: gli1 MO1 gli2 MO1 gli3 MO1

Article Images: [+] show captions
References [+] :
Agren, Expression of the PTCH1 tumor suppressor gene is regulated by alternative promoters and a single functional Gli-binding site. 2004, Pubmed