Olig2 regulates Purkinje cell generation in the early developing mouse cerebellum

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.

Zfp423/ZNF423 regulates cell cycle progression, the mode of cell division and the DNA-damage response in Purkinje neuron progenitors

“…1C,C′). A subset of ZFP423 PC progenitors also expresses the marker OLIG2, which is mostly associated with G0/G1 PC progenitors (Ju et al, 2016). Likewise, the domain containing differentiating PC precursors positive for CORL2 colocalizes Fig.…”

Maturation of Human Pluripotent Stem Cell-Derived Cerebellar Neurons in the Absence of Co-culture

“…On day 35, cells were already positive for OLIG2, CORL2, and BARHL1. OLIG2 is the earliest marker for Purkinje cells, and is associated with cell cycle exit and differentiation into postmitotic neurons (Takebayashi et al, 2002;Seto et al, 2014;Ju et al, 2016). CORL2 is specifically expressed in post-mitotic Purkinje cell precursors shortly after exiting the cell cycle (Minaki et al, 2008) and plays an essential role in Purkinje cell development (Wang et al, 2011;Nakatani et al, 2014).…”

“…Basally located cells further expressed PAX2 (Figures 2I,I' and Supplementary Figure S3F), which is a marker of GABAergic interneurons and their precursors in the developing cerebellum (Zhang and Goldman, 1996;Maricich and Herrup, 1999). Cells positive for OLIG2, a transcription factor expressed in neurogenic progenitors and nascent Purkinje cells (Seto et al, 2014;Ju et al, 2016), were also predominantly located in the basal layer ( Figures 2J,J' and Supplementary Figures S3G,G').…”

Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum

“…Lineage tracing suggested that other types of GABAergic VZ precursors also derive from Sox2 + eCSCs. We examined the expression of other VZ precursor markers, namely Olig2, which maintains the identity of PC progenitors 16 , and Lhx1/5, a marker for early GABAergic cells, in Psn KO mice and found that both were decreased, concomitantly with the increase in the number of Atoh1 + cells (Fig. S7C and S7D-H).…”