Drosophila anterior midgut internalization via collective epithelial-mesenchymal transition at the embryo surface and enclosure by surrounding tissues

Abstract

Internal organ development requires cell internalization, which can occur individually or collectively. The best characterized mode of collective internalization is epithelial invagination. Alternate modes involving collective mesenchymal behaviours at the embryo surface have been documented, but their prevalence is unclear. The Drosophila embryo has been a major model for the study of epithelial invaginations. However, internalization of the Drosophila anterior midgut primordium is incompletely understood. Here, we report that an epithelial-mesenchymal transition (EMT) occurs across the internalizing primordium when it is still at the embryo surface. At the earliest internalization stage, the primordium displays less junctional DE-cadherin than surrounding tissues but still exhibits coordinated epithelial structure as it invaginates with the ventral furrow. This initial invagination is transient, and its loss correlates with the activation of an associated mitotic domain. Activation of a subsequent mitotic domain across the broader primordium results in cell divisions with mixed orientations that deposit some cells within the embryo. However, cell division is non-essential for primordium internalization. Post-mitotically, the surface primordium displays hallmarks of EMT: loss of adherens junctions, loss of epithelial cell polarity, and gain of cell protrusions. Primordium cells extend over each other as they internalize asynchronously as individuals or small groups, and the primordium becomes enclosed by the reorganizations of surrounding epithelial tissues. We propose that collective EMT at the embryo surface promotes anterior midgut internalization through both inwardly-directed divisions and movements of its cells, and that the latter process is facilitated by surrounding tissue remodeling.