Lancaster, Courtney; (2025) Mechanisms of basal surface remodelling in epithelia. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Epithelia are evolutionary conserved tissues that form the structural foundation of most organs. A defining feature of epithelia is their apical (top)-basal (bottom) polarity, where each surface exhibits distinct structural and functional properties. During organogenesis, epithelial cells undergo dynamic shape changes that drive tissue morphogenesis, for example, branching in the developing lung. Morphogenesis has been extensively studied at the apical surface of epithelia, where cell shape changes and movements can be readily monitored with light microscopy. Much less is known about how cells coordinate remodelling of their basal surface. The basal surface is lined with a specialised extracellular matrix called the basement membrane, which must be accounted for to further understand how epithelial cells and tissues change shape during development. In this PhD thesis, I use the genetically tractable Drosophila retina to investigate mechanisms underlying basal surface remodelling during epithelial morphogenesis. I identify a morphogenetic pathway involving the Dystrophin glycoprotein complex (DGC), the extracellular matrix protein Laminin, and Integrins. I show that Laminin is patterned across the retinal extracellular matrix in a DGC dependent manner. These components direct Integrin accumulation at defined sites to enable cell attachment, thereby coordinating basal cell shape remodelling. Secondly, I present a new morphogenetic process that enables retinal thickening. Using genetics and a computational vertex model, I show that thickening of a curved epithelium requires coupling between basal surface contraction and cell elongation. Specifically, cell elongation is driven by Integrin and non-muscle myosin-II mediated basal contraction. Finally, I characterise a contractile machinery at the retinal basal surface which regulates basal surface contraction and exhibits muscle-like features. Together, these findings provide insights into the mechanisms of basal surface remodelling in epithelia. This works uncovers how spatially patterned extracellular cues contribute to cell geometry remodelling and highlights how coordinated morphogenetic processes generate three-dimensional tissue architecture during development.

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