Characterization of Olig2 expression during cerebellar development

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Highlights

  • Olig2 is expressed in the cerebellar ventricular zone at specific embryonic stages.

  • Olig2 is expressed in both neurogenic progenitors and nascent neurons.

  • Known proneural transcription factors each exhibit unique expression patterns.

  • Olig2 expression disappears prior to that of neuronal subtype-specific markers.

Abstract

The cerebellum is comprised of multiple GABAergic neuron subtypes whose complex interaction is central to its function. The molecular mechanisms underlying the diversity of the phenotypes of these neurons remain unclear. Transcription factors play important roles in many aspects of neural development from cell fate determination to neuronal maturation and maintenance of their phenotypes. Finding the fate determinants of each neuronal subtype would enable more detailed investigation of the mechanisms underlying the diversification of neurons. Previous work revealed many transcription factors that are expressed in the cerebellar ventricular zone, the origin of cerebellar GABAergic neurons during development, but definitive factors for each subtype of cerebellar GABAergic neurons remain unknown. Here, we report the expression pattern of basic-helix-loop-helix transcription factor Olig2 in the embryonic cerebellum. Olig2 is known to be involved in the development of not only oligodendrocytes but also some neurons. Immunohistochemistry revealed that Olig2 is expressed in progenitors for GABAergic neurons during embryonic day (E) 11.5 and E13.5, the peak period of Purkinje cell generation. Furthermore, co-immunostaining of several markers with Olig2 at E12.5 revealed that the Olig2-positive population consists of both neurogenic progenitors and nascent neurons. Olig2 is mostly co-expressed with the proneural transcription factors Ngn1/2 and cyclin-dependent kinase inhibitor p57KIP2 that are involved in cell cycle exit. Olig2-positive cells also express neural transcription factor NeuroD1, important for neuronal maturation, but not Corl2, the earliest marker for Purkinje cells. This expression pattern suggests that Olig2 may have an important role in the early stage of Purkinje cell development.

Section snippets

Olig2 is transiently expressed in the cerebellar VZ during specific developmental stages

To determine the expression period of Olig2 in the cerebellar VZ, we performed immunohistochemistry on embryonic cerebella at several developmental stages. Olig2 expression was detectable both in the VZ and parenchyma of the cerebellum. Olig2 in the VZ was detectable only during developmental stages E11.5  E13.5 (Fig. 1A–F). This period coincides with the peak period of Purkinje cell production (Hashimoto and Mikoshiba, 2003, Miale and Sidman, 1961, Sudarov et al., 2011). This result is

Discussion

In this study, we analyzed the expression pattern of Olig2 in the cerebellar VZ during early development. Olig2 was found to be expressed in Ptf1a-positive cells (progenitors for cerebellar GABAergic neurons) during a specific period around E11.5  E13.5, stages important for the generation of Purkinje cells (Hashimoto and Mikoshiba, 2003, Miale and Sidman, 1961, Sudarov et al., 2011).

Co-expression analysis of Ki67 and BrdU with Olig2 indicated that some populations of Olig2-positive cells were

Animals and immunohistochemistry

All animal experiments in this study have been approved by the Animal Care and Use Committee of the National Institute of Neuroscience, Japan. Embryos were fixed with 4% paraformaldehyde in PBS. Embryos embedded in OCT compound were cryosectioned at a thickness of 14 μm. Sections were treated with 0.5% BSA in PBS containing 0.2% Triton X-100 (blocking buffer) at room temperature for 1 h and subsequently incubated with antibodies listed below in blocking buffer at 4 °C for 20 h. Specimens were

Acknowledgement

We would like to thank Dr. Ruth Yu for comments. This work is supported by grants from the MEXT, Naito foundation, Intramural Research Grants (24-12, 25-3) for Neurological and Psychiatric Disorders of NCNP and Health Science Research Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H23-001) from the Japanese Ministry of Health, Labor and Welfare.

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