DROSOPHILA BETA(HEAVY)-SPECTRIN IS ESSENTIAL FOR DEVELOPMENT AND CONTRIBUTES TO SPECIFIC CELL FATES IN THE EYE

The spectrin membrane skeleton is a ubiquitous cytoskeletal structure with several cellular roles, including the maintenance of cell integri ty, determination of cell shape and as a contributor to cell polarity, We have isolated mutations in the gene encoding P-Heavy-spectrin in D rosophila, and have named this essential locus karst, karst mutant ind ividuals have a pleiotropic phenotype characterized by extensive larva l lethality and, in adult escapers, rough eyes, bent wings, tracheal d efects and infertility, Within karst mutant eyes, a significant number of ommatidia specifically lack photoreceptor R7 alongside more comple x morphological defects. Immunolocalization of P-Heavy-spectrin in wil d-type eye-antennal and wing imaginal discs reveals that P-Heavy-spect rin is present in a restricted subdomain of the membrane skeleton that colocalizes with DE-cadherin, We propose a model where normal levels of Sevenless signaling are dependent on tight cell-cell adhesion facil itated by the P-Heavy-spectrin membrane skeleton. Immunolocalization o f P-Heavy-spectrin in the adult and larval midgut indicates that it is a terminal web protein, but we see no gross morphological defects in the adult apical brush border in karst mutant flies, Rhodamine phalloi din staining of karst mutant ovaries similarly reveals no conspicuous defect in the actin cytoskeleton or cellular morphology in egg chamber s, This is in contrast to mutations in alpha-spectrin, the molecular p artner of P-Heavy-spectrin, which affect cellular structure in both th e larval gut and adult ovaries. Our results emphasize the fundamental contribution of the spectrin membrane skeleton to normal development a nd reveals a critical interplay between the integrity of a cell's memb rane skeleton, the structure of cell-cell contacts and cell signaling.