Developmental Evidence for the Evolutionary Relationship of Cerebellum and Cerebellum-like Structures in an Elasmobranch Fish

Abstract

The majority of neurons in the mammalian brain reside within the cerebellum. The cerebellum has several functions, including motor control, sensory processing and cognition. Despite its anatomical and functional significance, the evolutionary origins of the cerebellum are not well understood. There are several sensory nuclei present across vertebrate phylogeny collectively termed cerebellum-like structures due to a shared anatomy and physiology with the cerebellum. Common structure and function may arise due to a shared genetic and developmental toolkit. If this is true, the cerebellum may have evolved as a duplication or expansion of the cerebellum-like structures and these structures would be considered generatively homologous. In Chapter 1, I review what is known about cerebellar anatomy and development, cerebellum-like structures and candidate genes that may play a role in this common developmental genetic toolkit. In Chapter 2, I describe the morphological and temporal developmental relationships between the cerebellum and cerebellum-like structures in a representative of the most basal extant vertebrate lineage that possesses a cerebellum, the little skate Leucoraja erinacea. In Chapter 3, I test the hypothesis that the cerebellum and cerebellum-like structures develop using a shared developmental genetic toolkit by determining if homologs of candidate genes important for parallel-fiber-Purkinje cell synaptogenesis are expressed in the same respective cell types between both structures. I have also shown that major elements of gnathostome cerebellar development are conserved. Based on these findings, it is iii possible that the cerebellum evolved as a result of a duplication or expansion of the cerebellum-like developmental genetic toolkit.iv Acknowledgements I would first like to thank my advisor, David Bodznick, for his help during this thesis. David expertly managed this advisory role. I am extremely thankful that he let me make the mistakes that led to valuable learning experiences, while also being a safety net who subtly guided me toward this ultimate goal. I'm also thankful that David let me craft an unusual thesis, which involved methodologies and developmental questions that have not been tackled by this laboratory before.Due to the methodologies that were required to complete this thesis, I had to perform some work in the laboratory of other biologists at Wesleyan. I would like to thank Laura Grabel, Christopher Chen and Nickesha Anderson for teaching me how to perform immunohistofluorescence. Without taking up bench space in Laura's lab for several months I would not have been able to incorporate this methodology into our laboratory and this thesis would be very different. Nickesha, Chris and I started the PhD program in the same year and their friendship has been an important part of my tenure at Wesleyan. I would also like to thank Janice Naegele and Eric Weiss for teaching me how to perform western blots. I set up camp in the Naegele laboratory for several months while I performed this part of...