DSCAM regulates delamination of neurons in the developing midbrain

Nariko Arimura, Mako Okada, Shinichiro Taya, Ken Ichi Dewa, Akiko Tsuzuki, Hirotomo Uetake, Satoshi Miyashita, Koichi Hashizume, Kazumi Shimaoka, Saki Egusa, Tomoki Nishioka, Yuchio Yanagawa, Kazuhiro Yamakawa, Yukiko U. Inoue, Takayoshi Inoue, Kozo Kaibuchi, Mikio Hoshino

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

For normal neurogenesis and circuit formation, delamination of differentiating neurons from the proliferative zone must be precisely controlled; however, the regulatory mechanisms underlying cell attachment are poorly understood. Here, we show that Down syndrome cell adhesion molecule (DSCAM) controls neuronal delamination by local suppression of the RapGEF2-Rap1-N-cadherin cascade at the apical endfeet in the dorsal midbrain. Dscam transcripts were expressed in differentiating neurons, and DSCAM protein accumulated at the distal part of the apical endfeet. Cre-loxP-based neuronal labeling revealed that Dscam knockdown impaired endfeet detachment from ventricles. DSCAM associated with RapGEF2 to inactivate Rap1, whose activity is required for membrane localization of N-cadherin. Correspondingly, Dscam knockdown increased N-cadherin localization and ventricular attachment area at the endfeet. Furthermore, excessive endfeet attachment by Dscam knockdown was restored by co-knockdown of RapGEF2 or N-cadherin. Our findings shed light on the molecular mechanism that regulates a critical step in early neuronal development.

Original languageEnglish
Article numbereaba1693
JournalScience advances
Volume6
Issue number36
DOIs
Publication statusPublished - 09-2020

All Science Journal Classification (ASJC) codes

  • General

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