Spatial rearrangement of Purkinje cell subsets forms the transverse and longitudinal compartmentalization in the mouse embryonic cerebellum

Abstract

Transversely oriented lobules and longitudinally arrayed stripes of Purkinje cell subsets subdivide the cerebellar cortex into multiple compartments that are involved in diverse functions. In the mammalian cerebellum, anterior, and posterior lobules, which are involved in somatosensorimotor function, show an alternation of aldolase C (zebrin II) -positive and -negative stripes, whereas the central lobules (lobules VIb-VII and crus I), which are implicated in nonmotor functions, show a laterally expanded arrangement solely of aldolase C-positive stripes. To understand the developmental process of this compartmental pattern, we identified groups of Purkinje cell subsets in the entire mouse cerebellum at embryonic day (E) 14.5 by staining Purkinje cell subset markers. We then tracked four major domains of Protocadherin 10 (Pcdh10)-positive Purkinje cell subsets (medial, dorsal, central, and mid-lateral subsets), which were clearly demarcated during E14.5-17.5. These domains of Purkinje cell subsets shifted predominantly in the longitudinal direction to be positioned in the anterior and posterior lobules. However, a particular portion of the medial and mid-lateral domains, and the whole of the central domain shift in the lateral direction to be positioned in the central lobules. The results indicate that while the longitudinal shift of domains of Purkinje cell subsets forms the longitudinally striped compartments in the anterior and posterior cerebellum, the lateral shift of particular domains of Purkinje cell subsets underlies the laterally expanded arrangement of stripes in central lobules. Thus, the rearrangement of Purkinje cell subsets in the embryonic cerebellum is critically related to the compartmental organization in the mammalian cerebellum.

Cerebellar modules in the olivo‐cortico‐nuclear loop demarcated by pcdh10 expression in the adult mouse

“…In the adult, these stripes were either pcdh10 ‐positive or negative. Hence, we speculate that they generally express pcdh10 during the developmental stage (Vibulyaseck et al, ; see later section). Although the changes observed in the present study are presumed to be due to the lack of one allele of pcdh10 or due to the addition of neo gene in the genome of these mice, the mechanisms of how these changes occur are not clear.…”

“…As the expression pattern of Aldoc or zebrin II has been best described among these molecules, the expression of other molecules can be compared with that of Aldoc as was carried out in this study. The present study compared the expression pattern of pcdh10 directly to that of Aldoc, which has not been done in previous studies in the developing cerebellum (Neudert et al, ; Fujita & Sugihara, ; Vibulyaseck et al, ), by applying the method of SSAA (Vibulyaseck et al, ). The expression pattern of pcdh10 in the adult mouse, as clarified in this study, was a unique one, dissimilar to the expression pattern of any other molecule so far reported.…”

“…The expression pattern of pcdh10 in the adult mouse, as clarified in this study, was a unique one, dissimilar to the expression pattern of any other molecule so far reported. This pattern was also altered from the pcdh10 expression pattern in the developing cerebellum (Fujita & Sugihara, ; Vibulyaseck et al, ).…”

“…The knock‐in mouse line OL‐KO (Uemura, Nakao, Suzuki, Takeichi, & Hirano, ), which carries a transgene lacZ that codes for E. coli b‐galactosidase (b‐gal) protein replaced for the first exon of Pcdh10 gene (Uemura et al, ), was originally provided by Lexicon Pharmaceuticals (The Woodlands, TX). We maintained OL‐KO mice under B6C3F1 background (Vibulyaseck et al, ). Heterozygotes were identified by genotyping from a tail sample.…”

“…Here, we focused on expression of the pcdh10 gene which encodes the protein protocadherin 10 (Pcdh10), a member of the cadherin family of cell adhesion molecules. Heterogeneous pcdh10 expression pattern has been reported not only in Purkinje cells in the cerebellar cortex but also in neurons in the CN and in the IO during development till adulthood (Neudert et al, 2008;Fujita & Sugihara, 2012;Vibulyaseck et al, 2017). It has been suggested that pcdh10 expression may be involved in forming topography in axonal projections in CNS development (Aoki, Kimura, Suzuki, & Hirano, 2003;Hirano, Yan, & Suzuki, 1999;Neudert et al, 2008), due to the suggested homophilic adhesive function of cadherin family molecules (Brigidi & Bamji, 2011).…”