Cellular and molecular features of cerebellar evolution in primates
Date of Award
Spring 2022
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Interdepartmental Neuroscience Program
First Advisor
Sestan, Nenad
Abstract
Though the cerebellum has often been relegated to the sidelines in studying human cognition, recent evidence has revealed that human cerebellar evolution and development may play key roles in cognitive functioning. In this dissertation, I first examine the case for studying human cerebellar evolution and development and how this can inform not only our understanding of cerebellar circuits, but also the development of human cognition and, when this goes awry, neuropsychiatric disorders. Then, I present the first single-cell multiomics (RNA and ATAC sequencing) study of the cerebellum across primates, identifying key differentially expressed genes that may be associated with human and hominid great ape cerebellar specifications. These genes include ZP2 and EPHA6, expressed in cerebellar granule cells, as well as HS6ST3, and ZIC1, expressed in cerebellar astrocytes and Bergmann glia. I examine the function of ZP2 in human cerebellar granule cells as well as connect human-enriched features with cognition, focusing specifically on reading and language. Finally, I molecularly and cellularly characterize cerebellar organoids across four time-points to overcome limitations in the study of human-specific developmental features. I show and discuss organoid heterogeneity and identify potential signaling molecules for optimization of this method. Overall, these studies set the stage for investigating the contribution of cerebellar circuits to human cognition.
Recommended Citation
Cherskov, Adriana, "Cellular and molecular features of cerebellar evolution in primates" (2022). Yale Graduate School of Arts and Sciences Dissertations. 996.
https://elischolar.library.yale.edu/gsas_dissertations/996
