Force generated shaping of epithelial ducts

Hollow tubes and acini form the common units of most internal organs and they are essential for tissue function. However, virtually nothing is understood about the processes that engineer epithelia into these morphogenetic shapes. It is now recognised that mechanical forces originating both from within and outside cells contribute to tissue shaping. 

We will use the mammary gland system to determine how physical forces regulate tissue shape transformation. This tissue forms a network of collecting ducts connected to secretory alveoli, organised as a bi-layer of polarised luminal epithelia and myoepithelia. Basal myoepithelia are contractile in nature and form a dense coverage around ducts but sparsely subtend acini. We will determine whether a mechanical force generated by myoepithelial cells models the tubular shape of mammary ducts. Using primary 3D organoid cultures of breast epithelia that recapitulate polarised ducts and acini, combined with lentivirus gene knockdown and Cre-LoxP technology, we will perturb tension signalling from myoepithelia to determine their role. Live imaging and 3D-rendered data will be generated to build computational models that will be used in combination with experimental data to test future hypotheses.

This work will contribute significantly to solving key questions about mechanical control of branching morphogenesis.