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

Nicola K. Love, Nandaki Keshavan, Rebecca Lewis, William A. Harris, Michalis Agathocleous

Research output: Contribution to journalArticle

17 Scopus citations

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 mTORmediated mechanism. By contrast, the identity and proliferation of retinal stem cells are insensitive to ND and mTOR inhibition. Refeeding 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.

Original languageEnglish (US)
Pages (from-to)697-706
Number of pages10
JournalDevelopment (Cambridge)
Volume141
Issue number3
DOIs
StatePublished - Jan 1 2014

Keywords

  • Differentiation
  • Nutrient deprivation
  • Proliferation
  • Restriction point
  • Retina
  • Xenopus laevis
  • mTOR

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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