Olig2 regulates Purkinje cell generation in the early developing mouse cerebellum

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

doi:10.1038/srep30711

Jun Ju, Yuanxiu Liu + Show 9 more

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https://doi.org/10.1038/srep30711

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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.

Highlights

We show that Olig[2] is expressed in the late-phase of the VZ progenitor cell cycle and controls the rate of neurogenesis from cerebellar VZ progenitors, but not their proliferation
We found that DCX staining is prevalent in the cerebellar plate at this stage but absent from the rhombic lip (RL) and the VZ, the two major germinal zones of the developing cerebellum (Fig. 1B)
A 2-hour bromodeoxyuridine (5-bromo-2′-deoxyuridine, BrdU)-pulse labeling analysis showed that 25.2 ± 3.3% of the VZ Olig2+ cells are BrdU+ (Fig. 1D and arrow in 1D’) confirming that they are dividing progenitors, whereas the nuclear transitory zone (NTZ) Olig2+ cells are most BrdU− (Fig. 1D)

Summary

Introduction

We show that Olig[2] is expressed in the late-phase of the VZ progenitor cell cycle and controls the rate of neurogenesis from cerebellar VZ progenitors, but not their proliferation. Our long-term lineage tracing analysis indicates that Olig2+ progenitors give rise to PCs and DCN neurons, but rarely Pax2+ interneurons, challenging the “temporal identity transition” model of the cerebellar VZ progenitors that was recently proposed[15]

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