A nutrient-sensitive restriction point is active during retinal progenitor cell differentiation.
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.
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
Nicola K
NK
Love
Nandaki
N
Keshavan
Rebecca
R
Lewis
William A
WA
Harris
Michalis
M
Agathocleous
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002923:Cilia / Q000378:metabolism; D004789:Enzyme Activation; D005502:Food; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D012160:Retina / Q000166:cytology*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014982:Xenopus laevis; D015027:Zebrafish
D058570:TOR Serine-Threonine Kinases
Differentiation; Nutrient deprivation; Proliferation; Restriction point; Retina; Xenopus laevis; mTOR