UC Berkeley

Abstract

Establishing Planar Cell Polarity in an Edgeless Epithelium

By

Katherine Ruth Lipari

Doctor of Philosophy in Molecular and Cell Biology

University of California, Berkeley

Professor David Bilder, Chair

In all animals, organ function is dependent on two major processes that happen in the very beginning of embryonic development: differentiation and morphogenesis. In this study we focus on the process of morphogenesis, studying the planar cell polarity (PCP) pathway, a process that acts perpendicular to the apical-basal axis to orient the cell within the larger environment. From the elongation and closure of the entire central nervous system during neural tube closure, to the subtle orientation of hairs on the skin of a mammal, PCP dictates gross morphological events by first polarizing subcellular structures. Most of our knowledge about PCP derives from the Drosophila wing, where two well-characterized signaling pathways are currently known to regulate PCP: Fz/Vang PCP and Fat/Ds signaling. These two pathways have also been implicated in vertebrate PCP; despite vigorous investigation, there is a surprising paucity of data on how these pathways are shaping vertebrate organs, beyond the fact that they do. One major limitation is that PCP has been most deeply studied in organs with a fundamentally different topology than the tubules that make up the majority of animal organs. While planar polarization of proteins within the cells of the Drosophila wing align with the edge of the wing, causing elongation in the direction of polarization, vertebrate planar polarity proteins align perpendicular to later elongation and do not orient towards the edge of the tissue. Indeed, vertebrate tubular organs do not have similar edges to dictate orientation; they are ‘edgeless’ tissues. To study how planar polarization occurs in such structures we use the Drosophila egg chamber as a model. This tissue undergoes planar polarization perpendicular to the axis of elongation – similar to other tubule elongation – and depends upon the Fat2 cadherin for planar polarization and elongation. In this dissertation I show that planar polarization in this tissue is established early during development of the tissue – at the level of a few cells – by biased microtubule growth. This bias is then propagated by rotation of the entire tissue to create planar polarization of the overlying extracellular matrix to establish a persistent orientation as the tissue grows. I find novel genetic enhancers of the Fat2 mutant phenotype that identify genes involved in this early event and later morphogenetic events. I also study what cells within the epithelium itself are necessary for this rotation to occur. Overall, my thesis work has shown how planar polarization is established and propagated in edgeless tissues through tissue migration.