title: Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells.
abstract: Fragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs). We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3beta. Dysregulation of GSK3beta led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis.
authors.affiliation: Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Luo
authors.forename: Ge
authors.initials: G
authors.lastname: Shan
authors.forename: Weixiang
authors.initials: W
authors.lastname: Guo
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smrt
authors.forename: Eric B
authors.initials: EB
authors.lastname: Johnson
authors.forename: Xuekun
authors.initials: X
authors.lastname: Li
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Pfeiffer
authors.forename: Keith E
authors.initials: KE
authors.lastname: Szulwach
authors.forename: Ranhui
authors.initials: R
authors.lastname: Duan
authors.forename: Basam Z
authors.initials: BZ
authors.lastname: Barkho
authors.forename: Wendi
authors.initials: W
authors.lastname: Li
authors.forename: Changmei
authors.initials: C
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D051358:Cyclin-Dependent Kinase 4; D051860:Fragile X Messenger Ribonucleoprotein 1; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse
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