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Mitotic spindle orientation influences cell fate and notch signalling in chick neural tube
Author(s) -
G. N. Paliouras,
A. Aumont,
F. Barnabé-Heider,
K. J. L. Fernandes,
Santanu Banerjee,
Laura Gordon,
Thomas M. Donn,
Caterina,
Berti,
Cecilia B. Moens,
Steven J. Burden,
Michael Granato
Publication year - 2012
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2012.03.324
Subject(s) - neural tube , citation , mitosis , signalling , cell fate determination , biology , orientation (vector space) , notch signaling pathway , neuroscience , psychology , microbiology and biotechnology , computer science , library science , genetics , embryo , signal transduction , geometry , mathematics , transcription factor , gene
E-mail address: karl.jl.fernandes@umontreal.ca (K.J.L. Fernandes). The discovery of adult neural stem cells (NSCs) and adult neurogenesis has opened exciting new possibilities for promoting brain health and repair. An important step towards achieving this objective is deciphering the signalling pathways that control NSC activity under normal and pathological conditions. Here, we identify a critical role for mammalian target of rapamycin (mTOR) signalling in the biology of NSCs in the adult and aging brain. Using biochemical and immunohistochemical approaches, we show that mTOR signalling is highly activated within the subventricular zone (SVZ) stem cell niche of the adult forebrain. In primary cultures of forebrain NSCs, upregulation of mTOR signalling is essential for proliferation in response to growth factors. Moreover, inhibition of mTOR signalling in vivo causes a decline in the size of the proliferating cell population within the SVZ niche, indicating that mTOR signalling is required to maintain the endogenous NSC pool. Interestingly, when mTOR is inhibited in NSC cultures, the cells adopt a quiescent phenotype reminiscent of aging NSCs; furthermore, when mTOR signalling is stimulated in the aging brain using growth factors, proliferation of the quiescent NSCs is reactivated. These findings reveal key roles of the mTOR signalling pathway in the normal biology of adult NSCs, and suggest that stimulation of mTOR activity may be an approach for preventing or reversing agingassociated quiescence of brain stem cells. This work was supported by the Canadian Institutes of Health Research.