Msx genes delineate a novel molecular map of the developing cerebellar neuroepithelium

Abstract

AbstractIn the early cerebellar primordium, there are two progenitor zones, the ventricular zone (VZ) residing atop the IVthventricle and the rhombic lip (RL) at the lateral edges of the developing cerebellum. These zones give rise to the several cell types that form the GABAergic and glutamatergic populations of the adult cerebellum, respectively. Recently, an understanding of the molecular compartmentation of these zones has emerged. TheMsxgenes are a family of three transcription factors that are expressed downstream of Bone Morphogenetic Protein (BMP) signaling in these zones. Using fluorescent RNAin situhybridization, we have characterized theMsx(Msh Homeobox) genes and demonstrated that their spatiotemporal pattern segregates specific regions in the progenitor regions.Msx1andMsx2are compartmentalized within the rhombic lip (RL), whileMsx3is localized within the ventricular zone (VZ). The relationship of theMsxgenes with an early marker of the glutamatergic lineage,Atoh1, was examined inAtoh1-null mice and it was found that the expression ofMsxgenes persisted. Importantly,Msx1andMsx3expressions expanded in response to the elimination ofAtoh1. These results point to early markers of cerebellar progenitor zones and more importantly to an updated view of the molecular parcellation of the RL with respect to the canonical marker of the RL,Atoh1.