Elucidating polarity pathways in the fly and murine intestinal epithelium
Cell polarity is essential for normal cell function and for various developmental processes, such as axis determination, asymmetric stem cell divisions, and cell migration. Polarity is integral for tissue organization and failure in this process is a hallmark of human malignancies.
Extensive studies in diverse model systems have helped to establish recurring mechanisms that drive polarity in various cell types. Yet, these conserved polarity regulators are not universally required and it emerges that some cells use distinct polarity mechanisms in a context dependent manner. For example, the polarization of the Drosophila intestinal epithelium does not require any of the canonical polarity regulators, unlike all other well-characterized Drosophila epithelia. However, little is known about how this unconventional polarity is established.
This proposal aims to elucidate novel alternative polarity pathways in the intestinal epithelium of Drosophila. I will conduct a large--scale forward genetic screen to identify novel polarity regulators in the fly gut epithelium. Furthermore, I will examine the functional conservation of the newly identified polarity regulators in the murine intestinal stem cell organoids. Overall, this proposal will shed novel insights into the epithelial biology of the intestinal system.