A feedback loop between Paxillin and Yorkie sustains Drosophila intestinal homeostasis and regeneration

Dan Jiang, Pengyue Li, Yi Lu, Jiaxin Tao, Xue Hao, Xiaodong Wang, Wei Wu, Jinjin Xu, Haoen Zhang, Xiaoyu Li, Yixing Chen, Yunyun Jin () and Lei Zhang ()
Additional contact information
Dan Jiang: Shanghai Jiao Tong University
Pengyue Li: University of Chinese Academy of Sciences
Yi Lu: University of Chinese Academy of Sciences
Jiaxin Tao: University of Chinese Academy of Sciences
Xue Hao: University of Chinese Academy of Sciences
Xiaodong Wang: ShanghaiTech University
Wei Wu: University of Chinese Academy of Sciences
Jinjin Xu: Shanghai Jiao Tong University
Haoen Zhang: University of Chinese Academy of Sciences
Xiaoyu Li: University of Chinese Academy of Sciences
Yixing Chen: University of Chinese Academy of Sciences
Yunyun Jin: Shanghai Jiao Tong University
Lei Zhang: Shanghai Jiao Tong University

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract Balanced self-renewal and differentiation of stem cells are crucial for maintaining tissue homeostasis, but the underlying mechanisms of this process remain poorly understood. Here, from an RNA interference (RNAi) screen in adult Drosophila intestinal stem cells (ISCs), we identify a factor, Pax, which is orthologous to mammalian PXN, coordinates the proliferation and differentiation of ISCs during both normal homeostasis and injury-induced midgut regeneration in Drosophila. Loss of Pax promotes ISC proliferation while suppressing its differentiation into absorptive enterocytes (ECs). Mechanistically, our findings demonstrate that Pax is a conserved target gene of the Hippo signaling pathway in both Drosophila and mammals. Subsequent investigations have revealed Pax interacts with Yki and enhances its cytoplasmic localization, thereby establishing a feedback regulatory mechanism that attenuates Yki activity and ultimately inhibits ISCs proliferation. Additionally, Pax induces the differentiation of ISCs into ECs by activating Notch expression, thus facilitating the differentiation process. Overall, our study highlights Pax as a pivotal component of the Hippo and Notch pathways in regulating midgut homeostasis, shedding light on this growth-related pathway in tissue maintenance and intestinal function.

Date: 2025
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-55255-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55255-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-55255-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().