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

Research output: Contribution to journalArticle

44 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

Fingerprint

Cerebral Cortex
Neurons
Defects
Electroporation
Brain
Zinc Fingers
Neurogenesis
Brain Diseases
Locomotion
Cell Cycle
Transcription
Zinc
Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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

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, Hitoshi; Kasai, Masataka; Nakajima, Kazunori; Okado, Haruo.

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

Research output: Contribution to journalArticle

Ohtaka-Maruyama, C, Hirai, S, Miwa, A, Heng, JIT, 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
Ohtaka-Maruyama, Chiaki ; Hirai, Shinobu ; Miwa, Akiko ; Heng, Julian Ik Tsen ; Shitara, Hiroshi ; Ishii, Rie ; Taya, Choji ; Kawano, Hitoshi ; 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.
@article{bf11796d452441cb995645403512b26f,
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 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.",
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 Hitoshi Kawano and Masataka Kasai and Kazunori Nakajima and Haruo Okado",
year = "2013",
doi = "10.1016/j.celrep.2013.01.012",
language = "English",
volume = "3",
pages = "458--471",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",

}

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, Hitoshi

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 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.

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 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.

UR - http://www.scopus.com/inward/record.url?scp=84874236693&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874236693&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2013.01.012

DO - 10.1016/j.celrep.2013.01.012

M3 - Article

C2 - 23395638

AN - SCOPUS:84874236693

VL - 3

SP - 458

EP - 471

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 2

ER -