Elucidating function of the novel PINX1-related protein, Chigno, in reproductive stem cells and development

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PROJECT SUMMARY: The germline stem cell (GSC) niche functions to ensure continuous gamete production in organisms that reproduce sexually. Dysregulation of stem cells has also been linked to developmental disorders, cancer, infertility, and senescence. In flies and mammals alike, communication between GSCs and the surrounding soma regulates the balance between stem cell maintenance and differentiation. However, new and unexplored mechanisms regulating these processes are still being discovered - necessitating further enquiry. This proposal strives to elucidate the function of a novel PINX1-related protein, CG11180/Childless Gambino (Chigno), in regulating reproductive stem cell behavior and development in the fruit fly, Drosophila melanogaster. Chigno is a novel G-patch domain-containing protein in flies that is related to the mammalian tumor suppressor, PINX1. We previously identified Chigno as a binding partner of Chronologically inappropriate morphogenesis (Chinmo), a key regulator of somatic stem cell behavior in the adult Drosophila testis. Preliminary data collected by undergraduate and master’s student researchers in our lab show that Chigno is expressed in larval and adult testes, as well as Drosophila ovaries and early embryos. In adult testes, Chigno is observed specifically at the testis apex, which houses the germline stem cell (GSC) niche. Here, it is detected both in germ cells as well as somatic cyst stem cells (CySCs) and their progeny which regulate germline behavior. We also find that Chigno knockdown in adult CySCs and early cyst cells results in CySC over-production, formation of germ cell tumors, and an expansion of epithelial cells at the testis apex that may be linked to altered CySC identity. Furthermore, somatic Chigno depletion causes both testis and ovaries to become infertile. Experiments in this proposal are focused on understanding the role of Chigno in regulating testis stem cell self-renewal, differentiation, and cell fate maintenance (Aim 1), understanding Chigno protein function at the molecular level (Aim 2), and assessing whether Chigno functions in tissues other than the testis, including Drosophila ovaries and embryonic tissues (Aim 3). Given Chigno’s impact on fertility and testes stem cell behavior, as well as the diverse functions of G-patch/PINX1-related proteins in a range of cellular processes, the proposed studies into Chigno function hold great promise for elucidating novel mechanisms controlling fertility, stem cell behavior, and development in a range of organisms.