Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells.
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.
Luo
Yuping
Y
Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America.
Shan
Ge
G
Guo
Weixiang
W
Smrt
Richard D
RD
Johnson
Eric B
EB
Li
Xuekun
X
Pfeiffer
Rebecca L
RL
Szulwach
Keith E
KE
Duan
Ranhui
R
Barkho
Basam Z
BZ
Li
Wendi
W
Liu
Changmei
C
Jin
Peng
P
Zhao
Xinyu
X
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
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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