The sex and reproductive plasticity of intestinal muscles instruct gut size
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Alessandro Mineo Laura Blackie Alexandra Milona Emily Strachan Pedro Gaspar Nuno Miguel Luis Alvaro Castano-Medina Tomotsune Ameku Bryon Silva Anadika Prasad Clara L Essmann Jake Jacobson Todd Fallesen Vanessa Dao Sanjay Khadayate George Young Filipe Cabreiro Frank Schnorrer Irene Miguel-AliagaAbstract
Adult organs enlarge or regress in response to functional demands: changes commonly attributed to the dynamics of their resident stem cells. A striking example is the intestine, whose length varies with diet and reproductive status. We find that the size of the adult gut is extrinsically controlled by its surrounding muscles. In Drosophila, intestinal muscle differs in size and structure between sexes and grow in females during reproduction. By altering the sex or reproductive status of gut muscle cells, we establish that muscle-intrinsic sex determinants determine baseline sex differences in muscle myofibril width and organ size. Female muscles integrate hormonal and nutritional inputs during reproduction to elongate their sarcomeres; this reduces intestinal transit and further increases organ size. Such remodeling is adaptive and also occurs in mice. Our findings redefine the intestinal muscle as a responder to specific signals that adjust adult organ-level features and sustain reproductive demands.
Journal details
Journal
Cell
Volume
189
Issue number
19
Pages
6078-6096.e9
Available online
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Publisher website (DOI)
10.1016/j.cell.2026.07.024
Figshare
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Europe PubMed Central
42580334
Pubmed
42580334
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The publication was previously a preprint.
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