title: A network of heterochronic genes including Imp1 regulates temporal changes in stem cell properties.
abstract: 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. DOI: http://dx.doi.org/10.7554/eLife.00924.001.
authors.affiliation: Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Jinsuke
authors.initials: J
authors.lastname: Nishino
authors.forename: Sunjung
authors.initials: S
authors.lastname: Kim
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Morrison
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D025743:HMGA2 Protein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000502:physiology; D058953:Neural Stem Cells / Q000166:cytology*; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013687:Telencephalon / Q000378:metabolism
chemical_list: D025743:HMGA2 Protein; C579063:IMP1 protein, mouse; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C542687:mirnlet7 microRNA, mouse
keywords: cortical development; heterochronic gene; neural stem cell