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

Wado Akamatsu, Hiroaki Fujihara, Takayuki Mitsuhashi, Masato Yano, Shinsuke Shibata, Yoshika Hayakawa, Hirotaka James Okano, Shin Ichi Sakakibara, Hiroshi Takano, Toshiya Takano, Takao Takahashi, Tetsuo Noda, Hideyuki Okano

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133 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4625-4630
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number12
DOIs
Publication statusPublished - 2005 Mar 22

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Keywords

  • ELAV
  • Hu
  • Neural stem cell

ASJC Scopus subject areas

  • General

Cite this

Akamatsu, W., Fujihara, H., Mitsuhashi, T., Yano, M., Shibata, S., Hayakawa, Y., Okano, H. J., Sakakibara, S. I., Takano, H., Takano, T., Takahashi, T., Noda, T., & Okano, H. (2005). The RNA-binding protein HuD regulates neuronal cell identity and maturation. Proceedings of the National Academy of Sciences of the United States of America, 102(12), 4625-4630. https://doi.org/10.1073/pnas.0407523102