Date of Award
1-1-2023
Language
English
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
College/School/Department
Department of Biological Sciences
Content Description
1 online resource (xiii, 186 pages) : illustrations (some color)
Dissertation/Thesis Chair
Paolo E Forni
Committee Members
ChangHwan Lee, Melinda Larsen, Ravikumar Balasubramanian
Keywords
GnRH-1 neurons, Kallmann Syndrome, Olfactory Ensheathing Cells, Terminal Nerve, Olfactory nerve, Luteinizing hormone releasing hormone, Puberty
Subject Categories
Biology
Abstract
Sexual development and puberty are two key developmental processes that are crucial for the propagation and evolution of species. The hormone Gonadotropin releasing hormone-1 (GnRH-1) is a key hormone in regulating both processes by controlling the hormonal Hypothalamic-Pituitary-Gonadal axis in the release of sex hormones (Testosterone, Estrogen, Progesterone) at the correct developmental time points initiate puberty and progress sexual development. A subset of hypothalamic neurons known as the GnRH-1 neurons (GnRH-1ns) release GnRH-1 in a pulsatile fashion during embryonic and post-natal development to specifically regulate these processes. The GnRH-1ns are an interesting group of neurons because they are formed in the periphery, specifically the nose, and must migrate to the hypothalamus during mid-gestation. Disruptions in GnRH-1ns formation, migration, or signaling can lead to a human disorder known as hypogonadotropic hypogonadism (HH) that is characterized as an individual with low levels of GnRH-1 followed by decreased levels of pituitary gonadotropins and low sex hormones, which phenotypically leads to delayed or absent puberty. HH has two versions, normosmic idiopathic HH where only pubertal defects are seen or Kallmann Syndrome (KS) where pubertal defects co-segregate with olfaction defects. The close association of olfaction and puberty phenotypes as well as the developmental origin of the GnRH-1ns have led many to believe that GnRH-1ns migrate on the axons of the olfactory system. However, the relationship of GnRH-1ns and the olfactory system had not been thoroughly investigated. Furthermore, the migratory partner of the GnRH-1ns known as the Olfactory Ensheathing Cells (OECs) has not been thoroughly characterized during development.My doctoral research focused on understanding better the relationship of GnRH-1ns and the olfactory/vomeronasal/terminal nerve system and characterizing the developmental progression of the OECs. In the second and third chapters of my dissertation I discovered that the migration of the GnRH-1ns from the nose and the brain are independent of olfactory bulb formation and correct olfactory connections. I propose instead that the GnRH-1ns migrate on the axons of long forgotten nerve known as terminal nerve/nervus terminalis/cranial nerve 0. In the fourth and fifth chapters of my dissertation I identified two transcription factors, Ascl1 and Isl1, to be expressed by the neuronal progenitors of the GnRH-1ns, providing for the first-time markers to identify GnRH-1ns during early development. And lastly, in chapter 4 and chapter 6, I discovered the importance of a transcription factor, Gli3, in forming the OECs. Specifically, my data suggests that OECs are coming from a multipotent cell type known as Schwann Cell Precursors (SCPs) that are derived from the neural crest and can form many different cell types, including the many glia in the periphery. Furthermore, Gli3 may cell-autonomously regulate the transition of SCPs to OECs. My work has progressed the field substantially in better understanding the development and formation of both the GnRH-1ns and the OECs.
Recommended Citation
Taroc, Ed Zandro Moina, "Olfaction and puberty : the study of the development and migration of the GnRh-1ns and their migratory partners the olfactory unsheathing cells" (2023). Legacy Theses & Dissertations (2009 - 2024). 3253.
https://scholarsarchive.library.albany.edu/legacy-etd/3253
