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.
authors: Department of Brain Development and Neural Regeneration, Neural Development Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan. maruyama-ck@igakuken.or.jp
authors: Chiaki
authors: C
authors: Ohtaka-Maruyama
authors: Shinobu
authors: S
authors: Hirai
authors: Akiko
authors: A
authors: Miwa
authors: Julian Ik-Tsen
authors: JI
authors: Heng
authors: Hiroshi
authors: H
authors: Shitara
authors: Rie
authors: R
authors: Ishii
authors: Choji
authors: C
authors: Taya
authors: Hitoshi
authors: H
authors: Kawano
authors: Masataka
authors: M
authors: Kasai
authors: Kazunori
authors: K
authors: Nakajima
authors: Haruo
authors: H
authors: Okado
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000254:growth & development*; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C102938:Neurog2 protein, mouse; C520669:Zbtb18 protein, mouse