Id proteins synchronize stemness and anchorage to the niche of neural stem cells.

Published online

Journal Article

Stem-cell functions require activation of stem-cell-intrinsic transcriptional programs and extracellular interaction with a niche microenvironment. How the transcriptional machinery controls residency of stem cells in the niche is unknown. Here we show that Id proteins coordinate stem-cell activities with anchorage of neural stem cells (NSCs) to the niche. Conditional inactivation of three Id genes in NSCs triggered detachment of embryonic and postnatal NSCs from the ventricular and vascular niche, respectively. The interrogation of the gene modules directly targeted by Id deletion in NSCs revealed that Id proteins repress bHLH-mediated activation of Rap1GAP, thus serving to maintain the GTPase activity of RAP1, a key mediator of cell adhesion. Preventing the elevation of the Rap1GAP level countered the consequences of Id loss on NSC-niche interaction and stem-cell identity. Thus, by preserving anchorage of NSCs to the extracellular environment, Id activity synchronizes NSC functions to residency in the specialized niche.

Full Text

Duke Authors

Cited Authors

  • Niola, F; Zhao, X; Singh, D; Castano, A; Sullivan, R; Lauria, M; Nam, H-S; Zhuang, Y; Benezra, R; Di Bernardo, D; Iavarone, A; Lasorella, A

Published Date

  • April 22, 2012

Published In

Volume / Issue

  • 14 / 5

Start / End Page

  • 477 - 487

PubMed ID

  • 22522171

Pubmed Central ID

  • 22522171

Electronic International Standard Serial Number (EISSN)

  • 1476-4679

Digital Object Identifier (DOI)

  • 10.1038/ncb2490

Language

  • eng

Conference Location

  • England