Characterization of Olig2 expression during cerebellar development

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 p57(KIP2) 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.

Keywords: Cerebellum; GABAergic; Olig2; Purkinje cell; Transcription factor; Ventricular zone.