Somatic FGF non-autonomously regulates germline F-actin to control homeostasis, regeneration, and disease in the Drosophila testis

Abstract

A fundamental characteristic of life is the ability to reproduce and give rise to new offspring. Within the animal kingdom, sexual reproduction is nearly ubiquitous - requiring the generation and fusion of haploid germ cells, termed gametes (egg and sperm). The process of generating gametes, known as gametogenesis, is extremely conserved across animal phyla. Prior to meiosis and ploidy reduction, germ cells execute several rounds of mitotic expansion, or transit amplification (TA), while progressively differentiating. Ultimately, germline TA is responsible for generating a robust pool of functional gametes. Yet, germ cells do not execute differentiation in isolation. Germ cells rely on nearby somatic support cells to provide maintenance and instructional cues at all stages of differentiation. Despite this, somatic cells have never been shown to directly regulate germline TA. Here, we perform the first 24-hour longitudinal live imaging of germline transit amplification in the Drosophila testis. By combining our live imaging system with substantial genetic and pharmacological approaches, we outline a non-autonomous role for somatic cells in regulating germline TA. Outlined in this thesis are three key findings: (1) Somatic cells secrete the conserved growth factor, FGF (Pyramus), to promote germline FGFR (Heartless) and RC F-actin maintenance across reiterative TA divisions. (2) Attenuation of somatic FGF is required for germ cell de-differentiation following starvation. (3) Germline tumors induced by somatic cell transformation execute dysregulated TA divisions. Ultimately, our findings support a model whereby somatic cells promote homeostasis and transduce stress by regulating key germ cell biology.