Roles Of Histone Acetyltransferase Enok In Drosophila Germline Stem Cell Maintenance And Wing Vein Formation

Stem cells are self-renewing cells that have potential to differentiateinto different cell types. They have critical roles in various biologicalprocesses such as the development of multicellular organisms, tissuehomeostasis and organ regeneration. Maintenance of stem cells is largelydependent on the balance between their self-renewal and differentiation,which is controlled by multiple mechanisms both intrinsically andextrinsically. As a powerful in vivo system for studying stem cell and theniche, the Drosophila female germline stem cell (GSC) providesadvantages for revealing these mechanisms. It has been shown thatmaintaining the GSC population involves both genetic and epigeneticmechanisms. Although role of epigenetic regulation in the process isevident, the underlying mechanisms remain to be further explored. In thisstudy, we find that Enoki mushroom (Enok), a Drosophila putativeMYST family histone acetyltransferase controls GSC maintenance in theovary at multiple levels. First, removal or knockdown of Enok in thegermline causes a GSC maintenance defect. Further studies show that thecell-autonomous role of Enok in maintaining GSCs is not dependent on the BMP-Bam pathway and Nos/Pum complex. Interestingly, Bruno, anRNA binding protein, is ectopically expressed in the GSCs with Enokdeficiency. Misexpression of Bruno in germ cells results in GSC loss andprecocious differentiation of primordial germ cells. And there are geneticinteractions between bruno and enok in GSC maintenance. Therefore,Enok is likely to maintain GSC by inhibiting Bruno expression. In themeantime, we observe that Enok is non-autonomously required formaintaining GSCs. Compromised expression of enok in the niche cellsimpairs the GSC maintenance and BMP signal output. Althoughmolecular study imply that Enok regulates the diffusion of BMP ligands,the compromised BMP signal is not fully responsible for the GSCmaintenance defect caused by enok knockdown. Further studies show thatEnok in the niche functions in maintaining cap cells via Notch signaling,thereby contributing to GSC maintenance. This is the first demonstrationthat the niche size control requires an epigenetic factor. Taken together,these studies provide new insights into the GSC fate regulation.Besides regulates GSC maintenance in Drosophila ovaries, Enokalso controls wing vein formation in developing wings. CompromisingEnok in developing wings leads to ectopic vein formation in adult wings.This extra wing vein formation is closely related to the down-regulatedexpression of Dll, a transcription factor. The histone acetyltransferaseEnok probably controls the proper wing vein formation by regulating Dll expression, which expands our understanding in the function of histoneacetylation.