The interplay of atypical protein kinase C and actomyosin regulation in tissue mechanics and cell fate

Many tissues of our bodies are made of sheets of polarised epithelial cells.

During development, these features allow tissues to fulfil their physiological function and, during morphogenesis, to fold when individual groups of cells contract.

How exactly does the machinery that polarises cells intersect with actomyosin and how does contractility impinge on tissue and cellular behaviour? In the nervous system of flies, cell polarity and actomyosin regulation intersect driving cell fate decisions. During human corticogenesis, forces and actomyosin control cell behaviour and fate.

The signals regulating actomyosin and contractility in these contexts are unclear. aPKC, a key effector kinase of the polarisation machinery can negatively affect contractility by regulating Rho kinase. Our preliminary data suggest, however, that aPKC regulates actomyosin also through other pathways.

We have developed a strategy to screen for genes regulating contractility in Drosophila epithelia, based on a contractility assay induced by acute and specific aPKC inhibition.

We will further study the relationship between the cell polarity machinery and actomyosin regulation during human corticogenesis using iPS cell-derived neural rosettes.

This work could help understand corticogenesis’ regulation by mechanochemical signalling which, in the long term, could help find strategies against developmental disorders or neuronal degenerative diseases.