Cytological and transcriptional compartments in the cerebellum of the staggerer mouse

Abstract

The cerebellum exhibits a uniform histo‐ and cyto‐architecture. However numerous anatomical and biochemical studies have suggested that the cerebellum is highly compartmentalized in the mediolateral and rostrocaudal axes. In this review, we have focused on cytological and transcriptional compartmentalization which is unique to the cerebellum in the staggerer mouse. The staggerer mouse carries a deletion in the gene encoding the nuclear hormone receptor RORα, which results in severe impairments of phenotypic differentiation of cerebellar Purkinje cells (PC). This is characterized by reduced cell number, ectopia, smaller cell size and rudimentary dendrites without tertiary dendritic spines. Purkinje cells with different cytological features were distributed in discrete mediolateral regions within the staggerer cerebellum. Overlapping with the cytological compartments, PC with different levels for calbindin and inositol 1,4,5‐trisphosphate receptor type 1 mRNA, which are homogeneously expressed in adult wild‐type mice, form distinct transcriptional compartments. Furthermore, some compartments are associated with additional expression of NMDA receptor channel subunit mRNA which are absent in wild‐type PC. Although the unique compartmentalization observed in the staggerer cerebellum emerges as the result of RORα gene mutation, there are no mediolateral differences in the RORα expression itself in the wild‐type PC at any developmental stage. Thus, the formation of cytological and transcriptional compartments in the staggerer mouse should be ascxibed to RORα‐independent, cellular/molecular mechanisms which operate unevenly along the mediolateral cerebellar axis. With the cooperation of RORα‐dependent and ‐independent mechanisms, the PC attains full cytodifferentiation during cerebellar development.