Azlan Azali, Fukunaga Ryuya
bioRxiv. 2025 Jul 2:2025.07.01.662550. doi: 10.1101/2025.07.01.662550.
The self-renewal and differentiation of germline stem cells (GSCs) are tightly regulated during oogenesis. The female germline provides a powerful model to study these regulatory mechanisms. We previously identified Sakura (also known as Bourbon/CG14545) as a crucial factor for maintenance and differentiation of GSCs and oogenesis, and demonstrated that Sakura binds to Ovarian Tumor (Otu), another essential regulator of these processes. Here, we identify MYCBP (c-Myc binding protein) as an additional essential component of this regulatory network. We show that MYCBP physically associates with itself, Sakura, and Otu, forming binary and ternary complexes including a MYCBP•Sakura•Otu complex. MYCBP is highly expressed in the ovary, and null mutant females exhibit rudimentary ovaries with germline-less and tumorous ovarioles, fail to produce eggs, and are completely sterile. Germline-specific depletion of disrupts Dpp/BMP signaling, causing aberrant expression of ( ) and leading to defective differentiation and GSC loss. In addition, is required for female-specific splicing of ( ), a master regulator of sex identity determination. These phenotypes closely resemble those observed those of and mutants. Together, our findings reveal that MYCBP functions in concert with Sakura and Otu to coordinate self-renewal and differentiation of GSCs and oogenesis in .
生殖系干细胞（GSCs）的自我更新和分化在卵子发生过程中受到严格调控。雌性生殖系为研究这些调控机制提供了一个有力的模型。我们之前鉴定出Sakura（也称为Bourbon/CG14545）是GSCs维持、分化及卵子发生的关键因子，并证明Sakura与卵巢肿瘤（Otu）结合，Otu是这些过程的另一个重要调节因子。在此，我们鉴定出MYCBP（c-Myc结合蛋白）是这个调控网络的另一个重要组成部分。我们发现MYCBP与自身、Sakura和Otu发生物理相互作用，形成包括MYCBP•Sakura•Otu复合物在内的二元和三元复合物。MYCBP在卵巢中高表达，纯合突变雌性表现出卵巢发育不全，伴有无生殖系和肿瘤性卵巢小管，无法产卵，完全不育。生殖系特异性敲除会破坏Dpp/BMP信号通路，导致（ ）异常表达，进而导致分化缺陷和GSC丢失。此外，（ ）是性别身份决定的主要调节因子，其雌性特异性剪接需要MYCBP。这些表型与在（ ）和（ ）突变体中观察到的表型非常相似。总之，我们的研究结果表明，MYCBP与Sakura和Otu协同作用，以协调果蝇中GSCs的自我更新和分化以及卵子发生。
