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Chinmo是单个发育器官内差异性Hippo信号应答的一种新型调节因子。

Chinmo is a novel regulator of differential Hippo signaling response within a single developing organ.

作者信息

Tarikere Shreeharsha, Kumar Tarun, Ylla Guillem, Extavour Cassandra G

机构信息

Department of Organismic & Evolutionary Biology, Harvard University, Cambridge MA, USA.

Current address: Department of Human Genetics, McGill University, Montréal, Québec, Canada.

出版信息

bioRxiv. 2025 May 6:2025.05.02.651944. doi: 10.1101/2025.05.02.651944.

Abstract

Orchestrated control of proliferation of multiple cell types is essential for building a healthy organ. Here we use larval ovary development in as a model to understand the homeostasis of somatic and germ line cells in the formation of the female adult reproductive organ. We previously showed that the highly conserved Hippo signaling pathway regulates proliferation of both germ line and somatic cells in the larval ovary. Response to Hippo signaling appeared to be mediated by different genetic mechanisms in germ line and soma, but the mechanism allowing distinct responses to the same signaling pathway remained unknown. Here we perform cell type-specific RNA-Seq of isolated germ line and somatic cells from the developing ovary at multiple time points spanning the formation of germ line stem cell niches, in either a Hippo signaling loss- or gain-of-function genetic background. Applying network analysis to these data revealed a novel regulator of ovarian development, the transcription factor . Subsequent experimental validation showed that acts as a key germ cell-specific translator of Hippo signaling in the developing ovary, allowing the Hippo signal to be transduced in cell type-specific ways in germ line and somatic cells within the same organ.

摘要

多种细胞类型增殖的协调控制对于构建健康器官至关重要。在这里,我们以[具体物种]幼虫卵巢发育为模型,来理解雌性成体生殖器官形成过程中体细胞和生殖细胞的稳态。我们之前表明,高度保守的Hippo信号通路调节[具体物种]幼虫卵巢中生殖细胞和体细胞的增殖。生殖细胞和体细胞对Hippo信号的反应似乎由不同的遗传机制介导,但对同一信号通路产生不同反应的机制仍不清楚。在这里,我们在Hippo信号功能丧失或功能获得的遗传背景下,对发育中的卵巢在多个时间点分离的生殖细胞和体细胞进行细胞类型特异性RNA测序,这些时间点跨越了生殖干细胞微环境的形成。对这些数据进行网络分析揭示了一种新的卵巢发育调节因子,即转录因子[具体转录因子名称]。随后的实验验证表明,[具体转录因子名称]在发育中的卵巢中作为Hippo信号的关键生殖细胞特异性转导因子,使Hippo信号能够在同一器官内的生殖细胞和体细胞中以细胞类型特异性方式进行转导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ee6/12247949/9aeabcec71c3/nihpp-2025.05.02.651944v2-f0001.jpg

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