title: Id proteins synchronize stemness and anchorage to the niche of neural stem cells.
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.
authors.affiliation: Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Niola
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhao
authors.forename: Devendra
authors.initials: D
authors.lastname: Singh
authors.forename: Angelica
authors.initials: A
authors.lastname: Castano
authors.forename: Ryan
authors.initials: R
authors.lastname: Sullivan
authors.forename: Mario
authors.initials: M
authors.lastname: Lauria
authors.forename: Hyung-song
authors.initials: HS
authors.lastname: Nam
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Robert
authors.initials: R
authors.lastname: Benezra
authors.forename: Diego
authors.initials: D
authors.lastname: Di Bernardo
authors.forename: Antonio
authors.initials: A
authors.lastname: Iavarone
authors.forename: Anna
authors.initials: A
authors.lastname: Lasorella
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000235:genetics; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology*
chemical_list: D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins; D020690:GTPase-Activating Proteins; C464525:Id tumor-specific protein, mouse; C539504:Rap1GAP protein, mouse