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PMID: 15983404 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cooperative requirement of the Gli proteins in neurogenesis.

Development (Cambridge, England) ·Vol. 132 ·No. 14 ·2005-07-00 ·Pages 3267-79

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

Abstract

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.

MeSH Terms
Animals Gene Expression Regulation, Developmental/physiology Nervous System/embryology Neural Crest/embryology,metabolism Oligonucleotides, Antisense Oncogene Proteins/genetics,physiology RNA, Messenger/metabolism Receptors, Cell Surface/metabolism Trans-Activators Transcription Factors/genetics,physiology Xenopus Proteins/genetics,metabolism,physiology Xenopus laevis Zinc Finger Protein GLI1
Chemicals
Oligonucleotides, Antisense Oncogene Proteins PTCH1 protein, Xenopus RNA, Messenger Receptors, Cell Surface Trans-Activators Transcription Factors Xenopus Proteins Zinc Finger Protein GLI1
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Nguyen Vân
Department of Genetic Medicine and Development, 8242 CMU, 1 rue Michel Servet, University of Geneva Medical School, 1211 Geneva 4, Switzerland.
Chokas Ann L
Stecca Barbara
Ruiz i Altaba Ariel
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Article Info
Journal
Development (Cambridge, England)
Abbr.
Development
ISSN
0950-1991
DOI
10.1242/dev.01905
Published
2005-07-00
Pages
3267-79
Language
English
Region
England
NLM ID
8701744
PMCID
PMC1405824
Subset
IM
Grants
NINDS NIH HHS · R01 NS037352-08 · United States
External Links
PubMed source DOI: 10.1242/dev.01905 PMC Full Text View journal details
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