Morphological and molecular characterization of adult midgut compartmentalization in Drosophila . Nicolas Buchon^1,2, Dani Osman², Fabrice David², Jean-Philippe Boquete², Bart Deplancke², Bruno Lemaitre². 1) Cornell University, Ithaca, NY; 2) EPFL, Lausanne, Switzerland.

   The gut is a central organ of Eumetazoans and has critical roles both in health and disease. However our understanding of gut morphological and molecular features remains rudimentary, calling for integrative studies to understand its structure and function. In our study, we generated a comprehensive atlas of the Drosophila adult midgut based on analyses of microanatomy and of spatial transgene expression mapping along the gut. We uncovered a fine-resolution regional organization consisting of 14 sub-regions with distinct morphometric, histological and genetic characteristics. Further genomic analysis of the main gut regions revealed that immune, physiological and homeostatic properties also vary in those regions, suggesting functional compartmentalization. In addition, we showed that Drosophila intestinal regionalization is defined after adult eclosion, remains stable throughout life, and re-establishes following acute tissue damage, but is lost upon aging. Finally, we started to unravel the molecular determinants that control midgut compartmentalization, showing that regions are maintained by the interplay between pan-gut and regionalized transcription factors, in concert with the spatial activity of morphogens. Interestingly, disruption of midgut compartmentalization leads to intestinal disorders characterized by an increase in stem cell proliferation and aberrant immune responses. Together, our study analyzes Drosophila midgut compartmentalization in an integrative manner and provides new insights into the conserved mechanisms underlying intestinal regionalization in metazoans.