Date of Award

Fall 2023

Document Type

Open Access Dissertation

Department

Biological Sciences

First Advisor

Alissa Richmond-Armstrong

Abstract

Adult stem cell activity responds to organismal nutrient status to maintain and support tissue homeostasis. Despite the intricate relationship between dietary input, adipose tissue and peripheral organ function, we are at the tip of the iceberg regarding our understanding of the cellular and molecular mechanisms underlying adipose communication to other tissues. The Drosophila ovary receives nutritional signals from the fat body with multiple nutrient-sensing pathways functioning in adipocytes to control distinct stages of oogenesis. Insulin/insulin-like growth factor signaling (IIS) within adult adipocytes remotely controls oocyte production at distinct stages of oogenesis. The PI3K/Akt1 axis in adipocytes promotes germline stem cell maintenance via SGG, Drosophila GSK-3β, and early germline survival via an unidentified Akt1 target. Using adipocyte-specific manipulation of IIS pathway components, we find that a second axis downstream of the insulin receptor, the Ras/MAPK signaling pathway, acts within adipocytes to regulate adipocyte morphology and non-cell autonomously controls survival of early germline stem cell progeny and ovulation. Further work looking at GSK-3β substrates revealed that ATPCL, the Drosophila ortholog of human ACL, controls early germline cyst death. This dissertation sheds light on the complex physiological signaling networks that regulate stem cells and their progeny and molecular mechanisms involved interorgan communication. It is critical to decipher the molecular mechanisms linking adipocyte insulin signaling to remote control of tissues, like the ovary, considering the well-established link between obesity- induced adipocyte dysfunction and the pathophysiological properties of obesity- associated diseases, including, type-2 diabetes, multiple cancers, and polycystic ovarian syndrome.

Rights

© 2024, Tancia W. Bradshaw

Available for download on Wednesday, December 31, 2025

Included in

Biology Commons

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