Purkinje Cell Patterning—Insights from Single-Cell Sequencing

Abstract

Despite their homogeneous appearance, Purkinje cells are remarkably diverse with respect to their molecular phenotypes, physiological properties, afferent and efferent connectivity, as well as their vulnerability to insults. Heterogeneity in Purkinje cells arises early in development, with molecularly distinct embryonic cell clusters present soon after Purkinje cell specification. Traditional methods have characterized cerebellar development and cell types, including Purkinje cell subtypes, based on knowledge of selected markers. However, recent single-cell RNA sequencing studies provide vastly increased resolution of the whole cerebellar transcriptome. Here we draw together the results of multiple single-cell transcriptomic studies in developing and adult cerebellum in both mouse and human. We describe how this detailed transcriptomic data has increased our understanding of the intricate development and function of Purkinje cells and provides first clues into features specific to human cerebellar development.

Similar toxicity potential of glyphosate and glyphosate‐based herbicide on cerebellar development after maternal exposure in rats

“…In addition to the migration of granule cells during cerebellar development, the migration of Purkinje cell precursors outward from the ventricular zone and their alignment into a monolayer are required to form the three-layered cortical structure. 15 In the present study, we observed misaligned Purkinje cells that were exclusively immunoreactive with CALB1 in the GBH group at weaning, whereas the number of the Purkinje cells at this time was unchanged in the GBH group. Several in vivo studies using transgenic mice found that delayed migration of granule cells to the IGL disrupts the alignment of their synaptic partners, namely Purkinje cells.…”

“…Granule cells in the IGL outgrow axons and continue to grow the ML until the beginning of week seven after birth 13,14 . Purkinje cells are generated in the ventricular zone, where they proliferate and then migrate outward, eventually forming a single‐cell layer in the early postnatal period 15 . The cerebellum has a diverse distribution of interneurons, including basket/stellate cells in the ML and unipolar brush cells, Golgi cells, and Lugaro cells in the IGL/GL, which form a sophisticated neural network along with granule cells and Purkinje cells 16 …”

“…13,14 Purkinje cells are generated in the ventricular zone, where they proliferate and then migrate outward, eventually forming a single-cell layer in the early postnatal period. 15 The cerebellum has a diverse distribution of interneurons, including basket/stellate cells in the ML and unipolar brush cells, Golgi cells, and Lugaro cells in the IGL/GL, which form a sophisticated neural network along with granule cells and Purkinje cells. 16 In mammals, the vast majority of brain neurons are located in the cerebellum; for example, the cerebellum holds 70% of all brain neurons in rats.…”

Purkinje-Enriched snRNA-seq in SCA7 Cerebellum Reveals Zebrin Identity Loss as a Central Feature of Polyglutamine Ataxias

“…Based on single-cell studies, at least 4 “embryonic” clusters of PCs can be identified in the developing cerebellum with a specified set of marker genes unique to this developmental window 62 . Although SCA7 mice retain parasagittal striping of the cerebellum at 5 weeks of age, evidence for gene expression alterations in zebrin identity genes are already present at this time point ( Figure 4 ).…”

“…Based on single-cell studies, at least 4 "embryonic" clusters of PCs can be identified in the developing cerebellum with a specified set of marker genes unique to this developmental window 62 .…”