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XB-ART-48433
Development February 1, 2014; 141 (3): 697-706.

A nutrient-sensitive restriction point is active during retinal progenitor cell differentiation.

Love NK , Keshavan N , Lewis R , Harris WA , Agathocleous M .


Abstract
In many growing tissues, slowly dividing stem cells give rise to rapidly proliferating progenitors that eventually exit the cell cycle and differentiate. Growth rates are limited by nutrient availability, but it is unclear which steps of the proliferation-differentiation programme are particularly sensitive to fuel supplies. We examined how nutrient deprivation (ND) affects stem and progenitor cells in the ciliary marginal zone (CMZ) of the amphibian retina, a well-characterised neurogenic niche. We show that ND specifically blocks the proliferation and differentiation of progenitor cells through an mTOR-mediated mechanism. By contrast, the identity and proliferation of retinal stem cells are insensitive to ND and mTOR inhibition. Re-feeding starved retinas in vitro rescues both proliferation and differentiation, and activation of mTOR is sufficient to stimulate differentiation even in ND retinas. These results suggest that an mTOR-mediated restriction point operates in vivo to couple nutrient abundance to the proliferation and differentiation programme in retinal progenitor cells.

PubMed ID: 24449845
PMC ID: PMC3899821
Article link: Development
Grant support: [+]
Genes referenced: ascl1 atoh7 casp3.2 ccdc34 ccnd1 cdknx gnl3 herpud1 hes1 hes2 hes4 isl1 mtor myc mycn neurod1 neurod4 neurog1 neurog2 rax rps6 sox2
Antibodies: Rps6 Ab1 isl1 Ab2


Article Images: [+] show captions
References [+] :
Agathocleous, A directional Wnt/beta-catenin-Sox2-proneural pathway regulates the transition from proliferation to differentiation in the Xenopus retina. 2009, Pubmed, Xenbase


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