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, Hiroshi Kawano, Masataka Kasai, Kazunori Nakajima, Haruo Okado

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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 RP58(flox/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

Cite this

Ohtaka-Maruyama, C., Hirai, S., Miwa, A., Heng, J. I-T., Shitara, H., Ishii, R., ... 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
Ohtaka-Maruyama, Chiaki ; Hirai, Shinobu ; Miwa, Akiko ; Heng, Julian Ik-Tsen ; Shitara, Hiroshi ; Ishii, Rie ; Taya, Choji ; Kawano, Hiroshi ; Kasai, Masataka ; Nakajima, Kazunori ; Okado, Haruo. / RP58 regulates the multipolar-bipolar transition of newborn neurons in the developing cerebral cortex. In: Cell Reports. 2013 ; Vol. 3, No. 2. pp. 458 - 471.
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title = "RP58 regulates the multipolar-bipolar transition of newborn neurons in the developing cerebral cortex",
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 RP58(flox/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.",
author = "Chiaki Ohtaka-Maruyama and Shinobu Hirai and Akiko Miwa and Heng, {Julian Ik-Tsen} and Hiroshi Shitara and Rie Ishii and Choji Taya and Hiroshi Kawano and Masataka Kasai and Kazunori Nakajima and Haruo Okado",
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Ohtaka-Maruyama, C, Hirai, S, Miwa, A, Heng, JI-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, vol. 3, no. 2, pp. 458 - 471. https://doi.org/10.1016/j.celrep.2013.01.012

RP58 regulates the multipolar-bipolar transition of newborn neurons in the developing cerebral cortex. / Ohtaka-Maruyama, Chiaki; Hirai, Shinobu; Miwa, Akiko; Heng, Julian Ik-Tsen; Shitara, Hiroshi; Ishii, Rie; Taya, Choji; Kawano, Hiroshi; Kasai, Masataka; Nakajima, Kazunori; Okado, Haruo.

In: Cell Reports, Vol. 3, No. 2, 2013, p. 458 - 471.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - RP58 regulates the multipolar-bipolar transition of newborn neurons in the developing cerebral cortex

AU - Ohtaka-Maruyama, Chiaki

AU - Hirai, Shinobu

AU - Miwa, Akiko

AU - Heng, Julian Ik-Tsen

AU - Shitara, Hiroshi

AU - Ishii, Rie

AU - Taya, Choji

AU - Kawano, Hiroshi

AU - Kasai, Masataka

AU - Nakajima, Kazunori

AU - Okado, Haruo

PY - 2013

Y1 - 2013

N2 - 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 RP58(flox/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.

AB - 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 RP58(flox/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.

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