Project Details
Projekt
Gut formation through the heterotypic interaction of epithelial foregut and mesenchymal midgut precursor cells
Applicants
Professor Dr. Jörg Großhans; Professor Dr. Fred Wolf
Subject Area
Cell Biology
Biophysics
Developmental Biology
Biophysics
Developmental Biology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 564825356
The alimentary system of animals is constituted from ectodermal and endodermal derivatives, which together form a continuous tube from mouth to anus. During development ectodermal epithelia interact and fuse with endodermal tissue with epithelial or mesenchymal character depending on species. In Drosophila embryos, an epithelial foregut interacts with a mesenchymal midgut. Consequently, the fingerlike foregut tube opens towards the midgut, and the midgut acquires a secondary epithelial character aligned to the foregut epithelium. We hypothesize that the mesenchymal midgut cells form spot junctions with the foregut epithelium and among themselves consisting of E-cadherin complexes or other adhesion molecules. We hypothesize that the mesenchymal midgut cells invade the foregut epithelium from the basal side to consequently form a continuous layer of a primary foregut epithelium and secondary midgut epithelium. We identified candidate molecules for the interaction by single-cell transcriptomics of the interface cells. Candidates will be tested by localization of the proteins and functionally by genetic interference. The distribution and structure of E-cadherin spot junctions and their associated components will be investigated by high resolution confocal microscopy and DNA-PAINT nanoscopy. The morphodynamics of the interface will be analysed by live imaging and 3D quantification of cell shape dynamics, for which novel computational tools will be applied such as spherical harmonics decomposition. The physiological relevance of the heterotypic epithelial-mesenchymal interaction will be tested in embryos either lacking the epithelial part of the interface (foregut-less embryos) or containing an epithelial-epithelial interface (mesenchyme-less embryos).
DFG Programme
Priority Programmes
