Male-specific development of the germline stem cell niche regulated by doublesex and fruitless

Sex determination;Biology

Zhou, HongSpradling, Allan ;

Johns Hopkins University

关键词: Sex determination;    Biology;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/60109/ZHOU-DISSERTATION-2018.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

In Drosophila melanogaster, sexual development of the male and female gonads is controlled by the key sex-specific transcription factor Doublesex (Dsx). While homologs of Dsx are known to control gonad development in virtually all animals, the molecular mechanism remains largely unknown. Previously, we took genomic and bioinformatic approaches to identify Dsx targets genome-wide. fruitless (fru) was identified as a candidate target of Dsx involved in male gonad development. fru, like dsx, is regulated by sex-specific alternative splicing to promote male-specific mating behaviors. Surprisingly, we found that male-specific Fru expression in the gonad does not depend on sex-specific alternative splicing. Instead, dsx is necessary and sufficient to activate Fru expression in the gonad. Further, our Dsx occupancy data and enhancer-reporter analyses support that Dsx directly regulates transcription from the fru P4 promoter. A key step in establishing gonadal sex is the formation of sexually-dimorphic germline stem cell (GSC) niche. Important components of the niche, named terminal filaments (TFs) in females and hubs in males, are different in morphology and molecular marks, yet originate from a shared pool of progenitor cells. Previously, we proposed that dsx regulates male-specific niche development by inhibiting hub-to-TFs trans-differentiation during the 3rd instar larval stage. Here we report that fru functions downstream of dsx in this process. Loss of dsx causes Fru expression to be reduced and variable in the gonad. Niche sex reversal occurs when the Fru level in dsx gonads is below a threshold. We further show that fru is sufficient to block TF formation and masculinize the niche when expressed in wildtype ovaries, but loss of fru is insufficient to induce gonad sex reversal.The male GSC niche is maintained throughout adulthood for continuous spermatogenesis. We show that fru is not required to prevent sexual cell-fate reprogramming in the male niche and insufficient to masculinize the female niche in adults. Instead, fru functions in the cyst stem cells to anchor the hub at the testis apex and maintain CySC self-renewal. fru also is required to regulate proper spermatogenesis through promoting cyst cell survival and differentiation.In summary, we discovered a previously unrecognized branch of the Drosophila sex determination pathway, where the master regulator of the behavior dimorphism functions downstream of dsx to regulate male-specific development of the gonad stem cell niche. This study highlights the interaction between sex-determining genes of the CNS and the gonad, and provide insight into the evolution of the sex determination pathway.