RP58 Regulates the Multipolar-Bipolar Transition of Newborn Neurons in the Developing Cerebral Cortex

Chiaki Ohtaka-Maruyama, Shinobu Hirai, Akiko Miwa, Julian Ik Tsen Heng, Hiroshi Shitara, Rie Ishii, Choji Taya, Hitoshi Kawano, Masataka Kasai, Kazunori Nakajima, Haruo Okado

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46 Citations (Scopus)

Abstract

Accumulating evidence suggests that many brain diseases are associated with defects in neuronal migration, suggesting that this step of neurogenesis is critical for brain organization. However, the molecular mechanisms underlying neuronal migration remain largely unknown. Here, we identified the zinc-finger transcriptional repressor RP58 as a key regulator of neuronal migration via multipolar-to-bipolar transition. RP58-/- neurons exhibited severe defects in the formation of leading processes and never shifted to the locomotion mode. Cre-mediated deletion of RP58 using in utero electroporation in RP58flox/flox mice revealed that RP58 functions in cell-autonomous multipolar-to-bipolar transition, independent of cell-cycle exit. Finally, we found that RP58 represses Ngn2 transcription to regulate the Ngn2-Rnd2 pathway; Ngn2 knockdown rescued migration defects of the RP58-/- neurons. Our findings highlight the critical role of RP58 in multipolar-to-bipolar transition via suppression of the Ngn2-Rnd2 pathway in the developing cerebral cortex.

Original languageEnglish
Pages (from-to)458-471
Number of pages14
JournalCell Reports
Volume3
Issue number2
DOIs
Publication statusPublished - 2013 Feb 8

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Ohtaka-Maruyama, C., Hirai, S., Miwa, A., Heng, J. I. T., Shitara, H., Ishii, R., Taya, C., Kawano, H., Kasai, M., Nakajima, K., & Okado, H. (2013). RP58 Regulates the Multipolar-Bipolar Transition of Newborn Neurons in the Developing Cerebral Cortex. Cell Reports, 3(2), 458-471. https://doi.org/10.1016/j.celrep.2013.01.012