Building and breaking epithelial integrity in the neural tube: an optogenetic approach

Most organs in the body arise from tube-like structures made from specialised polarised cells called epithelial cells. These cells have a strict apico-basal orientation; they align their apical ends along a centrally located lumen. It is thought that apico-basal polarity defects might play an early role in tissue disruption when diseases such as cancer are developing.

I will use an optogenetic approach that uses light to reversibly manipulate subcellular polarity protein location and signalling in a developing zebrafish neural tube in vivo. This will allow me to directly test how the polarity of individual cells drives the organisation of a whole organ. I will alter cell polarity and division to test how these processes are aligned during growth. I will also alter the cancer-linked PI3K signalling pathway to determine whether dysregulation of apico-basal polarity is a cause or consequence of tissue disruption.

My findings will provide information on the cellular mechanisms of disease initiation.