Journal Article

Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum

Miyashita, Satoshi, Yamada, Mayumi, Masuyama, Norihisa, Inoue, Takayoshi, Magnuson, Mark A., Ikenaka, Kazuhiro, Kumai, Minoru, Ono, Yuichi, Ishiwata, Shin’ichi, Taya, Shinichiro, Minaki, Yasuko, Takebayashi, Hirohide, Hoshino, Mikio, Hamaguchi, Akiko, Wright, Christopher V., Kawaguchi, Yoshiya, Nakatani, Tomoya, Inoue, Yukiko U., Campbell, Kenneth, Fujiyama, Tomoyuki, Chapman, Heather, Seto, Yusuke

2014

Overview

In the cerebellum, all GABAergic neurons are generated from the Ptf1a-expressing ventricular zone (Ptf1a domain). However, the machinery to produce different types of GABAergic neurons remains elusive. Here we show temporal regulation of distinct GABAergic neuron progenitors in the cerebellum. Within the Ptf1a domain at early stages, we find two subpopulations; dorsally and ventrally located progenitors that express Olig2 and Gsx1, respectively. Lineage tracing reveals the former are exclusively Purkinje cell progenitors (PCPs) and the latter Pax2-positive interneuron progenitors (PIPs). As development proceeds, PCPs gradually become PIPs starting from ventral to dorsal. In gain- and loss-of-function mutants for Gsx1 and Olig1/2 , we observe abnormal transitioning from PCPs to PIPs at inappropriate developmental stages. Our findings suggest that the temporal identity transition of cerebellar GABAergic neuron progenitors from PCPs to PIPs is negatively regulated by Olig2 and positively by Gsx1, and contributes to understanding temporal control of neuronal progenitor identities. GABAergic neuron progenitors in the cerebellum give rise to Purkinje cells and GABAergic interneurons. Here the authors show that the transcription factors Olig2 and Gsx1 regulate an identity transition from Purkinje cell progenitors to interneuron progenitors during mouse development.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/378/2571/2579 / 631/378/2632/1368 / 64/60 / Animals / Basic Helix-Loop-Helix Transcription Factors - metabolism / Brain / Cells, Cultured / Cerebellum - cytology / Cerebellum - metabolism / Developmental biology / Developmental stages / Engineering / GABAergic Neurons - cytology / GABAergic Neurons - metabolism / Humanities and Social Sciences / Immunohistochemistry / Interneurons - cytology / Interneurons - metabolism / Mice / multidisciplinary / Nerve Tissue Proteins - metabolism / Neurobiology / Neurons / Neurosciences / Oligodendrocyte Transcription Factor 2 / Physiology / Purkinje Cells - cytology / Purkinje Cells - metabolism / Science / Science (multidisciplinary) / Stem Cells - cytology / Stem Cells - metabolism / Subpopulations / Transcription factors / Transcription Factors - metabolism