The RNA-binding protein HuD regulates neuronal cell identity and maturation

被引：176
作者：
Akamatsu, W
Fujihara, H
Mitsuhashi, T
Yano, M
Shibata, S
Hayakawa, Y
Okano, HJ
Sakakibara, S
Takano, H
Takano, T
Takahashi, T
Noda, T
Okano, H [1 ]
机构：
[1] Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan
[2] Keio Univ, Sch Med, Dept Microbiol, Tokyo 1608582, Japan
[3] Keio Univ, Sch Med, Dept Pediat, Tokyo 1608582, Japan
[4] Dokkyo Univ, Sch Med, Dept Histol & Neurobiol, Mibu, Tochigi 3210293, Japan
[5] Tohoku Univ, Sch Med, Dept Mol Genet, Sendai, Miyagi 9808575, Japan
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2005年 / 102卷 / 12期
关键词：
ELAV; Hu; neural stem cell;
D O I：
10.1073/pnas.0407523102
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页码：4625 / 4630
页数：6
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