Basic molecular fingerprinting of immature cerebellar cortical inhibitory interneurons and their precursors

While the development of cerebellar granule and Purkinje neurons has been extensively studied, little is known about the developmental mechanisms that lead to the generation and diversification of inhibitory GABAergic interneurons of the cerebellar cortex. To address this issue, we compared gene expression in complete, early postnatal murine cerebella to that in cerebella from which immature inhibitory interneurons and their precursors had been stripped based on their expression of green fluorescent protein (GFP) from the Pax2 locus. We identified some 300 candidate genes selectively enriched within immature cerebellar cortical inhibitory interneurons and/or their precursors, many of which were also expressed in their adult descendants and/or the embryonic cerebellar ventricular epithelium that gives rise to these cells. None of the genes identified, among them Tcfap2alpha, Tcfap2beta, Lbxcor1 and Lbx1, was cell-type specific. Rather, gene expression, and also splicing, changed dynamically during development and rather reflects stage of differentiation than lineage. Consistently, cluster analysis of transcriptional regulators and genes specific for adult cerebellar GABAergic cells does not suggest a hierarchical lineage relationship or an early commitment of subtypes of cerebellar cortical inhibitory interneurons. Together, these data support the notion that diversification of cerebellar inhibitory interneurons is highly regulative and subject to local signaling to postmigratory precursors.