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Title: Development of the chick hypothalamus
Author: Fu, Sheung Ching
ISNI:       0000 0004 6061 3140
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2016
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The hypothalamus in the ventral forebrain is critical to homeostasis. In comparison to other regions of the CNS, its development is poorly understood. In particular there is ongoing debate regarding the relationship of the hypothalamus with the telencephalon versus the diencephalon, regarding the influence of the prechordal mesoderm on the hypothalamus, and regarding development of particular hypothalamic subdomains. Many of the issues arise because we do not, currently, have a basic understanding of the origins of the hypothalamus, i.e. the position of hypothalamic progenitors in the early neural tube. As yet, not study has systematically fate-mapped hypothalamic progenitors in the early chick neural tube. However, previous fate mapping studies in our lab have shown that a region that is widely accepted to harbour thalamic progenitors will actually give rise to hypothalamic cells. Having a better, and accurate, understanding of where hypothalamic precursors are situated at early neural tube stages and their relative position to neighbouring tissues is a critical first step in understanding the development of the hypothalamus. In this study, I identify the position of ventral midline hypothalamic precursors in the Hamburger and Hamilton stage (HH)10 chick embryo using fluorescent lipophilic dyes to systematically fate map the ventral midline of the prosencephalon. I demonstrate that the prevalent model of hypothalamic origins at HH10 is incorrect. My studies begin to identify differential migration/movement of adjacent cell populations that help us better understand morphogenesis of the hypothalamus. Further, my studies allow me to address the molecular signature of hypothalamic progenitors. Analysis of markers that define distinct subdomains in the developed (E3-E5) hypothalamus reveals that the anterior and tuberal hypothalamus cannot be distinguished at HH10. This has prompted me to propose a novel model of hypothalamic development, in which the hypothalamus is initially tuberal in character, the anterior and mammillary hypothalamus developing subsequently from tuberal progenitors. Finally, preliminary studies suggest a role for Shh in development of anterior hypothalamic cells from tuberal progenitors: pharmacological blockade of Shh signalling over a narrow time window leads to disrupted differentiation and growth of the anterior hypothalamus. Tuberal progenitors accumulate abnormally, and the infundibulum and Rathke's pouch fail to develop normally. Together my study builds on earlier work showing that Shh is required for hypothalamic induction. It shows a critical later role for Shh signalling in growth and differentiation of the neurogenic anterior hypothalamus and in the formation of the tuberal infundibulum, a domain that will orchestrate development of the pituitary gland, a critical brainbody interface.
Supervisor: Placzek, Marysia ; Towers, Matthew Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available