The cerebellum is compartmentalized into some tens of areas that have distinct axonal projection patterns, and thus that are presumably involved in different functions. In each compartment, a subset of Purkinje cells will have distinct expression levels of certain molecules, such as aldolase C (=zebrin II), which can be used as markers for the compartment. Because aldolase C is expressed only in the mature cerebellum, we investigated whether protocadherin 10 (Pcdh10), which is expressed during cerebellar development, could also act as a molecular marker. By using heterozygote samples of the knock-in mouse strain (OL-KO, Lexicon Pharmaceuticals, Inc., USA; Uemura et al., 2007), in which Pchd10 gene expression is visualized by the reporter molecule beta-galactosidase, we were able to follow the evolution of cerebellar compartments through successive developmental stages.
Whole mount preparations of the cerebellum from embryonic day 13.5 up to adult were used to investigate the alternating striped pattern of Pcdh10 expression throughout development. In the adult cerebellar cortex, high expression areas were clearly compartmentalized into multiple longitudinal stripes. Although these compartments could be roughly traced through development, they were differently organized in shape and were merged in some cases in the immature cerebellum (down to E13.5). Consequently, the appearance of the mature striped pattern of Pcdh10 expression in the adult cerebellum was quite different from that in the embryonic immature cerebellum. We are now investigating the details of the developmental changes in Pcdh10 compartments.
We also compared Pcdh10 compartments and Aldolase C compartments precisely in serial sections at postnatal day 16, when Aldolase C compartments start to stabilize, and at adult. We are studying the spatial relationship between Aldolase C and Pcdh10 compartments. Initial results suggest that the compartments defined by these markers are exactly matched in some areas but not in others.
The results indicate that the fine molecular compartments of the adult cerebellar cortex have a developmental lineage from immature early compartments in the embryonic cerebellum.