Nutrient-responsive midgut turnover is spatially controlled by serotonin signaling

Abstract

Barrier epithelia undergo rapid turnover, yet how spatial tissue heterogeneity and environmental cues shape turnover rates remains poorly understood. Here, we show that serotonin signaling spatially regulates homeostatic turnover of the Drosophila midgut epithelium in a nutrient-responsive manner. Organ-wide analysis revealed regions of constitutively high and low turnover, as well as areas whose renewal depends on nutrient intake. In rapidly renewing posterior regions, serotonin accumulates in enterocytes undergoing programmed cell death (erebosis) in response to nutrient availability. Serotonin signals through the conserved 5HT7 receptor to promote enteroblast (EB) maturation and migration-associated morphological changes. 5HT7 signaling is both necessary and sufficient for renewal in high-turnover regions, and its sustained disruption leads to epithelial multilayering. Mechanistically, 5HT7 signaling regulates genes involved in metabolic pathways, such as the serine biosynthesis pathway, and in the actin cytoskeleton, which drive EB maturation and morphological change, respectively. Together, our findings establish a signaling mechanism that links nutritional cues to the spatial regulation of barrier epithelium turnover.

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BibTeX RIS

BibTeX

@misc{lamichane2026nutrientresponsive,
  title = {{Nutrient-responsive midgut turnover is spatially controlled by serotonin signaling}},
  author = {N. Lamichane and P. Borgman and T. Rintakangas and K. Gaertner and M. Robciuc and O. Deniz and T. Kirkinen and C. Biehler and S. Andersson and J. Barlund and O. Kinnunen and P. Katajisto and J. Mattila and V. Hietakangas},
  howpublished = {bioRxiv},
  year = {2026},
  month = nov,
  doi = {10.64898/2026.11.03.763885},
  url = {https://www.biorxiv.org/content/10.64898/2026.11.03.763885v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Nutrient-responsive midgut turnover is spatially controlled by serotonin signaling
AU  - N. Lamichane
AU  - P. Borgman
AU  - T. Rintakangas
AU  - K. Gaertner
AU  - M. Robciuc
AU  - O. Deniz
AU  - T. Kirkinen
AU  - C. Biehler
AU  - S. Andersson
AU  - J. Barlund
AU  - O. Kinnunen
AU  - P. Katajisto
AU  - J. Mattila
AU  - V. Hietakangas
PY  - 2026
DA  - 2026/11/03
PB  - bioRxiv
DO  - 10.64898/2026.11.03.763885
UR  - https://www.biorxiv.org/content/10.64898/2026.11.03.763885v1
AB  - Barrier epithelia undergo rapid turnover, yet how spatial tissue heterogeneity and environmental cues shape turnover rates remains poorly understood. Here, we show that serotonin signaling spatially regulates homeostatic turnover of the Drosophila midgut epithelium in a nutrient-responsive manner. Organ-wide analysis revealed regions of constitutively high and low turnover, as well as areas whose renewal depends on nutrient intake. In rapidly renewing posterior regions, serotonin accumulates in enterocytes undergoing programmed cell death (erebosis) in response to nutrient availability. Serotonin signals through the conserved 5HT7 receptor to promote enteroblast (EB) maturation and migration-associated morphological changes. 5HT7 signaling is both necessary and sufficient for renewal in high-turnover regions, and its sustained disruption leads to epithelial multilayering. Mechanistically, 5HT7 signaling regulates genes involved in metabolic pathways, such as the serine biosynthesis pathway, and in the actin cytoskeleton, which drive EB maturation and morphological change, respectively. Together, our findings establish a signaling mechanism that links nutritional cues to the spatial regulation of barrier epithelium turnover.
ER  -

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