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Title: Cerebellar development and the origins of foliation in birds and reptiles
Author: Varela, Tristan
ISNI:       0000 0004 8505 3653
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2019
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The cerebellum is the rostral-most structure of the vertebrate hindbrain, comprised chiefly of granule cells (GC) and Purkinje cells (PC), and characterised by a range of different forms. Factors that determine the size, shape and degree of foliation of the cerebellum are poorly understood. The clade Reptilia, which also includes all extant birds, presents a model to explore this phenomenon, due to the morphological variety within its member species: A highly folded cerebellum in birds, tripartite in crocodilians, and completely smooth in turtles and snakes. To explore the developmental factors underlying this variety, different representative species of reptiles were investigated and found to exhibit varying patterns of GC progenitor (GCP) proliferation in the external granule layer (EGL) - a transient structure that forms during the development of the tetrapod cerebellum. A mitotic EGL is present in birds, alligators, and snakes, but not in turtles, suggesting that this phenomenon arose in the amniotic ancestor and was eventually lost in the chelonian lineage. Shh, which has a pro-mitotic role for the EGL in mammals, is present in the cerebellum of all reptilians, although a detailed analysis for components of the Shh signalling pathway in the chicken cerebellum suggests that it may not have a mitogenic role. Ex ovo electroporation of turtle cerebellar explants suggests that within the EGL, the differentiation factor NeuroD1 is coexpressed with the GCP marker, Atoh1. However, experimental disruption of NeuroD1 within the EGL does not stimulate proliferation but interferes with GCP viability and migration. While the degree of proliferation within a given EGL might be hypothesised to drive species-specific patterns of cerebellar folding, by contrast, it is developmental gradients of Purkinje cells that appear to be closely correlated with the degree of foliation in a given cerebellum. In all, this work demonstrates some of the mechanisms underlying the cerebellar development of organisms that were previously unsurveyed, as well providing novel insight as to the developmental origins of the cerebellum.
Supervisor: Wingate, Richard James Tobias ; Tucker, Abigail Saffron Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available