Identification of a novel transcriptional corepressor, Corl2, as a cerebellar Purkinje cell-selective marker.

The developmental origin of cerebellar Purkinje cells (PCs) has not been precisely mapped and the genetic program of the specification of this neuronal subtype is largely unknown. Here, we report the isolation of a novel mouse gene encoding a transcriptional corepressor, Corl2, and its expression pattern. Corl2 expression was restricted to the central nervous system in both adult and embryonic stages. In situ hybridization and immunohistochemistry using a polyclonal antibody against Corl2 revealed that Corl2 is selectively expressed at high levels in the developing cerebellum, ventral metencephalon and myelencephalon at E12.5. In these brain regions, neural progenitors did not express Corl2 during the proliferative state but started to express it shortly after exit from the cell cycle. In the cerebellum, Corl2 was specifically expressed in PCs at the adult stage, and consistently, most Corl2(+) cells expressed PC markers, such as RORalpha and calbindin, at the late embryonic stage. At E12.5, when PCs are emerging, GABAergic neurons generated from the dorsal part of the Ptf1a(+) progenitor domain selectively expressed Corl2. Importantly, Corl2(+) cells in the cerebellum did not express the GABAergic interneuron marker Pax2 at any of the developmental stages. Collectively, these results strongly suggest that Corl2 is a specific marker for PCs in the cerebellum from their emergence until the adult stage. Furthermore, this marker was useful for unmasking the precise origin of PCs and delineating the domain map within the ventricular zone that generates cerebellar GABAergic neurons.