Panel A shows that enteroendocrine cells (EEs) exist in two morphological forms: open-type EEs, which extend an apical projection into the gut lumen to directly sense luminal contents, and closed-type EEs, which are fully embedded within the epithelium and lack luminal access. Panel B shows that open-type EEs express high levels of smooth septate junction (sSJ) genes and are capable of luminal sensing, leading to EE activation. In contrast, closed-type EEs express higher levels of transcription factors Ptx1 and escargot (esg) and do not perform luminal sensing. Experimental overexpression of Ptx1 or esg, or knockdown of sSJ genes, converts open-type EEs into closed-type EEs, impairing their activation and secretory function. Panel C shows that both mammalian and Drosophila intestines contain similar open- and closed-type EE configurations, demonstrating that EE morphology, epithelial positioning, and functional roles are evolutionarily conserved across species.
EE morphology is genetically controlled, functionally relevant, and conserved across species. (A) Open-type EEs extend an apical protrusion into the gut lumen, whereas closed-type EEs are embedded within the epithelium without luminal access. (B) Open-type EEs highly express sSJ genes, while closed-type EEs highly express transcription factors, Ptx1 and esg. Overexpression of Ptx1 or esg, or knockdown of sSJ genes, converts open-type EEs into closed-type ones, thereby impairing luminal sensing and peptide secretion. (C) Similar open- and closed-type EE configurations are observed in both mammalian and Drosophila intestines, suggesting that EE morphology and epithelial positioning are evolutionarily conserved.