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A regional regulatory axis shapes enteroendocrine cell morphology and function

2026/03/31 by Haimeng Yu, Yongchao Zhang, Jingyuan Shi +5 · 2 voices
Immunology and Microbiology · Neuroscience · Biochemistry, Genetics and Molecular Biology · #Invertebrate Immune Response Mechanisms #Neurobiology and Insect Physiology Research #Developmental Biology and Gene Regulation

paper · doi:10.1083/jcb.202506084

openalex publication_date 2026/03/31 · openalex created_date 2026/04/01 · openalex updated_date 2026/07/16

Abstract

Enteroendocrine cells (EEs) are secretory cells in the gut epithelium that exist in two morphologically distinct forms: "open" and "closed." However, the mechanisms governing this morphological divergence remain unclear. Here, we show that in the adult Drosophila midgut, open-type EEs are the predominant form throughout most regions, whereas the closed type is found exclusively in the middle gastric region (R3). We identify Ptx1, a region-specific transcription factor, as a key determinant of the closed EE morphology. Ptx1 maintains the expression of the Snail-family transcription factor escargot (esg) in newly formed EEs, which in turn suppresses the expression of smooth septate junction (sSJ) genes. This repression prevents apical integration into the epithelium, resulting in the formation of closed-type EEs. Ectopic expression of ptx1 or esg in non-R3 regions induces the formation of closed-type EEs, which exhibit impaired sensing of dietary amino acids. Together, our findings reveal a regional transcriptional regulatory axis that controls EE morphology and its associated luminal sensing function.

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