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Stem cell properties change over time to match the changing growth and regeneration demands of tissues. We showed previously that adult forebrain stem cell function declines during aging because of increased expression of  let-7  microRNAs, evolutionarily conserved heterochronic genes that reduce HMGA2 expression. Here we asked whether  let-7  targets also regulate changes between fetal and adult stem cells. We found a second  let-7  target, the RNA binding protein IMP1, that is expressed by fetal, but not adult, neural stem cells. IMP1 expression was promoted by Wnt signaling and Lin28a expression and opposed by  let-7  microRNAs.  Imp1 -deficient neural stem cells were prematurely depleted in the dorsal telencephalon due to accelerated differentiation, impairing pallial expansion. IMP1 post-transcriptionally inhibited the expression of differentiation-associated genes while promoting the expression of self-renewal genes, including  Hmga2 . A network of heterochronic gene products including Lin28a,  let-7 , IMP1, and HMGA2 thus regulates temporal changes in stem cell properties.

A network of heterochronic genes including Imp1 regulates temporal changes in stem cell properties