title: FMRP regulates the transition from radial glial cells to intermediate progenitor cells during neocortical development.
abstract: During vertebrate cortical neurogenesis, radial glial cells (RGCs) serve as neural stem cells that generate neurons directly or indirectly through intermediate progenitor cells (IPCs). The transition from RGCs to IPCs is a key step in determining overall neuronal production and may underlie evolutionary expansion of the cerebral cortex. Here we show that this transition is controlled by fragile X mental retardation protein (FMRP), an RNA-binding protein whose deficiency causes fragile X syndrome. Analysis of mouse embryos electroporated with FMRP small hairpin RNA and knock-out mouse embryos lacking FMRP reveals that specific loss of FMRP causes depletion of neocortical RGCs due to an RGC-to-IPC cell fate change. The RGC depletion is associated with altered F-actin organization and can be largely rescued by overexpressing profilin 1 (Pfn1), a core actin regulatory protein promoting F-actin formation. Our data suggest that FMRP suppresses the transition from RGCs to IPCs during neocortical development by an actin-dependent mechanism.
authors.affiliation: Department of Neurosurgery, Boston Medical Center, Boston, MA 02118, USA.
authors.forename: Roya
authors.initials: R
authors.lastname: Saffary
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xie
mesh_terms: D000199:Actins / Q000648:ultrastructure; D000818:Animals; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019579:Neocortex / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis; D009457:Neuroglia / Q000166:cytology*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000199:Actins; D051860:Fragile X Messenger Ribonucleoprotein 1; D034741:RNA, Small Interfering; C497684:Fmr1 protein, mouse