Id proteins synchronize stemness and anchorage to the niche of neural stem cells
Author: ["Francesco Niola","Xudong Zhao","Devendra Singh","Angelica Castano","Ryan Sullivan","Mario Lauria","Hyung-song Nam","Yuan Zhuang","Robert Benezra","Diego Di Bernardo","Antonio Iavarone","Anna Lasorella"]
Publication: Nature Cell Biology
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Abstract
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. Iavarone, Lasorella and colleagues develop genetic mouse models to study the roles of inhibitor of DNA-binding (Id) proteins in neural stem-cell maintenance. They show that Id proteins promote neural stem-cell adhesion to their niche by driving the transcriptional repression of Rap1GAP, thereby maintaining the activity of the Rap1 GTPase, a known regulator of integrin adhesion.
Cite this article
Niola, F., Zhao, X., Singh, D. et al. Id proteins synchronize stemness and anchorage to the niche of neural stem cells. Nat Cell Biol 14, 477–487 (2012). https://doi.org/10.1038/ncb2490
