THU580 A Subset Of Migrating Cells Co-express Gonadotropin Releasing Hormone And Prokineticin Receptor 2 During Embryonic Development

Abstract

Abstract Disclosure: A.E. Danku: None. C.F. Elias: None. A subset of migrating cells co-express gonadotropin releasing hormone and prokineticin receptor 2 during embryonic development Antoinette Danku and Carol F Elias. Neuroscience Graduate Program and Department of Molecular & Integrative Physiology, University to Michigan. Reproductive vitality in humans is strongly influenced by developmental foundations. The successful migration of GnRH cells and the pulsatile secretion of gonadotropin releasing hormone (GnRH) drives pubertal onset and dictates long-term fertility outcomes. During development, GnRH neurons migrate from the nasal placode to the basal forebrain to reach their destination in the medial preoptic area (MPOA). Aberrant GnRH migration causes redirection of axonal projections to atypical brain regions and dysregulated GnRH secretion. Disruption of GnRH neuronal function causes infertility or reproductive dysfunction. These etiologies are grouped as isolated gonadotropin deficiencies (IGD). Kallmann’s syndrome (KS) is a pediatric IGD that manifests as anosmia and hormonal dysfunction that can result in pubertal delay or infertility. Children with KS often have mutations in prokineticin 2 (Prok2) or the cognate receptor (ProkR2).Prok2 and ProkR2 are required for the formation of the olfactory bulb in rodents and humans. Loss-of-function mutations in these genes also disrupts GnRH cell migration, but whether the activation of ProkR2 regulates the guidance of GnRH neurons to their final destination has not been defined. Previous studies suggested that GnRH and ProkR2 are expressed in distinct cells, but how the prokineticin system may alter GnRH migration is largely unknown. To gain insights into the underlying mechanisms associated with ProkR2-GnRH interaction and migration, we conducted single nuclei RNA sequencing in nasal-forebrain junction of embryos at embryonic day 16 (E16) and fluorescent in situ hybridization in three developmental time points: E14, E16, and E18 for validation and spatial evaluation. Using these methods, we were able to isolate GnRH and ProkR2 cells and sort their cell types into clusters. While these cells differ in their expression profiles, they both express genes associated with migration at E16. Our findings suggest that ProkR2 cells in the nasal-forebrain junction migrate along with GnRH cells. Additionally, a subset of these migrating cells co-express ProkR2 and GnRH mRNA. Further studies are needed to determine whether this subset of cells take on specialized roles in GnRH cell migration and maturation. Presentation: Thursday, June 15, 2023