Our long-term goal is to understand the genetic control of morphogenesis at the interface between the cellular and tissue levels. We use planar polarity in the Drosophila wing as a model system. A similar planar polarity is involved in the convergent extension movements of vertebrate gastrulation and for the function of a number of adult epithelia. For example, the epithelial cells that line our respiratory tract have apical cilia that beat in a polarized manner. The Drosophila wing contains about 30,000 cells, each of which produces a single distally pointing cuticular hair. Our genetic analysis showed that the frizzled signaling/signal transduction pathway regulates hair polarity by controlling the subcellular location for hair morphogenesis. The frizzled pathway has both cell autonomous and cell non-autonomous components. An early step in the cell autonomous pathway is the accumulation of several proteins including Frizzled along the distal edge of the cell. This leads to the cytoskeleton being activated so that a hair forms at the distal most part of the cell. The function of the Inturned and Fuzzy proteins is required to couple the distal accumulation of Fz to the cytoskeleton. Our hypothesis is that Inturned and Fuzzy serve as adapter proteins. We will test this by identifying proteins that interact with Inturned and Fuzzy. Mutations in the recently cloned fritz gene produce wing phenotypes that are indistinguishable from inturned and fuzzy. We will continue the molecular genetic analysis of fritz and determine if this protein is part of a complex with Inturned and Fuzzy. We will use time-lapse confocal microscopy to examine the kinetics of accumulation of proteins at the distal edge of wing cells and if this is altered in mutants. During the past period of support, we identified a transcription factor encoding gene where mutations give rise to a polarity phenotype. Genetic strategies will be used to determine if this gene is a downstream component of the frizzled pathway. Mutations in several genes that encode cadhenn domain containing proteins give rise to planar polarity phenotypes. For one of these genes we will determine the relative importance of adhesion versus signal transduction for the mutant phenotype.
Showing the most recent 10 out of 18 publications
