Studying cell sorting during Drosophila abdominal morphogenesis. How is positional information encoded?

Abstract

A fundamental developmental question is how cells adopt distinct positions in greatly complex but precisely organised tissues. There have been significant advances in our understanding of how different fates of cells are specified during development. However, how fate information determines the positioning of cells is still elusive. During the Drosophila adult abdominal epidermis morphogenesis, diploid histoblasts replace the larval epithelial cells and eventually adopt different fates along the anterior-posterior (A-P) axis¹. Changing the histoblasts’ fates in clones of cells by altering the Hedgehog pathway leads to cell sorting, where clonal cells position themselves according to their new fate. We combined Drosophila genetics to produce genetic mosaics with in vivo 4D microscopy to study histoblast sorting. Live recordings of the mutant clones revealed that they utilize changes in both their cytoskeleton and junctions in order to sort. Mutant clones in the posterior compartments can merge with anterior cells by cell intercalating from the posterior compartment and sort out towards the anterior compartment where cells possess similar fates to the clones. Labelling of the cytoskeleton of histoblasts showed that sorting mutant Hedgehog cells have increased actin levels, which may alter the surface tension cells and contribute to their sorting. Interestingly, labelling of the protrusions of the cells revealed that mutant clones can establish temporal connections with each other based on long-thick basal protrusions, that may provide information to the clones about more favourable regions in the tissue. Lastly, based on the molecular screening conducted in this study, it was found that the planar cell polarity molecules Dachsous/Fat and two Toll receptors Toll-2/Toll-8 can alter cell affinities among the histoblasts. This leads to the hypothesis that the different cell fates defined by Hedgehog translate to different positional information encoded by differential expression of the four adhesion molecules Fat, Dachsous, Toll-2, and Toll-8.

Date of Award	14 Jun 2023
Original language	English
Awarding Institution	University of St Andrews
Supervisor	Marcus Bischoff (Supervisor) & Judith Sleeman (Supervisor)