Cooperative requirement of the Gli proteins in neurogenesis.
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.
Nguyen
Vân
V
Department of Genetic Medicine and Development, 8242 CMU, 1 rue Michel Servet, University of Geneva Medical School, 1211 Geneva 4, Switzerland.
Chokas
Ann L
AL
Stecca
Barbara
B
Ruiz i Altaba
Ariel
A
D000818:Animals; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D009420:Nervous System / Q000196:embryology*; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism; D016376:Oligonucleotides, Antisense; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis; D000071676:Zinc Finger Protein GLI1
D016376:Oligonucleotides, Antisense; D015513:Oncogene Proteins; C426851:PTCH1 protein, Xenopus; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D000071676:Zinc Finger Protein GLI1