TY - JOUR T1 - Common origin of the cerebellar dual somatotopic areas revealed by tracking embryonic Purkinje cell clusters with birthdate tagging JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0251-20.2020 SP - ENEURO.0251-20.2020 AU - Khoa Tran-Anh AU - Jingyun Zhang AU - Viet Tuan Nguyen-Minh AU - Hirofumi Fujita AU - Tatsumi Hirata AU - Izumi Sugihara Y1 - 2020/10/14 UR - http://www.eneuro.org/content/early/2020/10/14/ENEURO.0251-20.2020.abstract N2 - One of the notable characteristics of the functional localization in the cerebellar cortex is the dual representation of the body (somatotopy) along with 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 five 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.Significance statement Genetically programmed morphogenetic processes in the embryonic brain can form a highly organized anatomical complex in the postnatal brain. The adult cerebellum has a complex functional localization; one of the challenging aspects of which is the dual representation of somatosensorimotor function in both the anterior and posterior paravermal areas. To elucidate morphogenetic processes of the intricate organization of the cerebellar cortex, we tracked lineages of early cerebellar PC clusters by birthdate-tagging methods. Starting with nine clusters at embryonic day 14.5, we clarified the differentiation of lineage of all clusters in later stages. Our results indicate that the spatial differentiation of embryonic PC clusters is involved in forming the basic cerebellar organization of the mouse brain. ER -