Common Origin of the Cerebellar Dual Somatotopic Areas Revealed by Tracking Embryonic Purkinje Cell Clusters with Birthdate Tagging.

Abstract

One of the notable characteristics of the functional localization in the cerebellar cortex is the dual representation of the body (somatotopy) on its anterior-posterior axis. This somatotopy is conspicuous in the C1/C3 module, which is demarcated as the multiple zebrin-negative and weekly-positive stripes in dual paravermal areas in anterior and posterior lobules within the cerebellar compartments. In this report, we describe the early formation process of the cerebellar compartmentalization, particularly in the C1/C3 module. As developing PCs guide formation of the module-specific proper neuronal circuits in the cerebellum, we hypothesized that the rearrangement of embryonic Purkinje cell (PC) clusters shapes the adult cerebellar compartmentalization. By identifying PC clusters with immunostaining of marker molecules and genetical birthdate-tagging with Neurog2-CreER (G2A) mice, we clarified the three-dimensional spatial organization of the PC clusters and tracked the lineage relationships among the PC clusters from embryonic day 14.5 (E14.5) till E17.5. The number of recognized clusters increased from 9 at E14.5 to 37 at E17.5. Among E14.5 PC clusters, the c-l (central-lateral) cluster which lacked E10.5-born PCs divided into six c-l lineage clusters. They separately migrated underneath other clusters and positioned far apart mediolaterally as well as rostrocaudally by E17.5. They were eventually transformed mainly into multiple separate zebrin-negative and weakly-positive stripes, which together configured the adult C1/C3 module, in the anterior and posterior paravermal lobules. The results indicate that the spatial rearrangement of embryonic PC clusters is involved in forming the dual somatotopic areas in the adult mouse paravermal cerebellar cortex.