The RNA-binding protein HuD regulates neuronal cell identity and maturation.
Neural Hu proteins (HuB/C/D) are RNA-binding proteins that have been shown to induce neuronal differentiation activity when overexpressed in immature neural progenitor cells or undifferentiated neuronal tumors. Newly generated HuD-deficient mice exhibited a transient impaired-cranial-nerve-development phenotype at an early embryonic stage. Adult HuD-deficient mice exhibited an abnormal hind-limb reflex and poor rotarod performance. Analysis of neurosphere formation revealed that the number and self-renewal capacity of the neural stem/progenitor cells were increased in HuD-deficient mice. HuD-deficient primary neurospheres also generated a smaller number of neurons. Cohort analysis of the cellular proliferative activity by using BrdUrd and iododeoxuridine labeling revealed that the number of differentiating quiescent cells in the embryonic cerebral wall was decreased. Long-term administration of BrdUrd revealed that the number of slowly dividing stem cells in the adult subventricular zone was increased in the HuD-deficient mice. Taken together, the results suggest that HuD is required at multiple points during neuronal development, including negative regulation of proliferative activity and neuronal cell-fate acquisition of neural stem/progenitor cells.
Akamatsu
Wado
W
Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Fujihara
Hiroaki
H
Mitsuhashi
Takayuki
T
Yano
Masato
M
Shibata
Shinsuke
S
Hayakawa
Yoshika
Y
Okano
Hirotaka James
HJ
Sakakibara
Shin-Ichi
S
Takano
Hiroshi
H
Takano
Toshiya
T
Takahashi
Takao
T
Noda
Tetsuo
T
Okano
Hideyuki
H
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D003391:Cranial Nerves / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D004247:DNA / Q000235:genetics; D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; D018390:Gene Targeting; D051379:Mice; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; C498011:Elavl4 protein, mouse; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D004247:DNA