Olig2 regulates Purkinje cell generation in the early developing mouse cerebellum

Olig2 调节小鼠小脑早期发育中浦肯野细胞的生成

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作者:Jun Ju, Qian Liu, Yang Zhang, Yuanxiu Liu, Mei Jiang, Liguo Zhang, Xuelian He, Chenchen Peng, Tao Zheng, Q Richard Lu, Hedong Li

Abstract

The oligodendrocyte transcription factor Olig2 plays a crucial role in the neurogenesis of both spinal cord and brain. In the cerebellum, deletion of both Olig2 and Olig1 results in impaired genesis of Purkinje cells (PCs) and Pax2(+) interneurons. Here, we perform an independent study to show that Olig2 protein is transiently expressed in the cerebellar ventricular zone (VZ) during a period when PCs are specified. Further analyses demonstrate that Olig2 is expressed in both cerebellar VZ progenitors and early-born neurons. In addition, unlike in the ganglionic eminence of the embryonic forebrain where Olig2 is mostly expressed in proliferating progenitors, Olig2(+) cells in the cerebellar VZ are in the process of leaving the cell cycle and differentiating into postmitotic neurons. Functionally, deletion of Olig2 alone results in a preferential reduction of PCs in the cerebellum, which is likely mediated by decreased neuronal generation from their cerebellar VZ progenitors. Furthermore, our long-term lineage tracing experiments show that cerebellar Olig gene-expressing progenitors produce PCs but rarely Pax2(+) interneurons in the developing cerebellum, which opposes the "temporal identity transition" model of the cerebellar VZ progenitors stating that majority of Pax2(+) interneuron progenitors are transitioned from Olig2(+) PC progenitors.

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