168 Oral - Patterning and Morphogenesis II
Saturday April 09, 10:30 AM - 10:45 AM

Authors:
Guangxia Miao; Li Guo; Denise Montell

Affiliation: University of California-Santa Barbara

Keywords:
p. cell migration; b. cell polarity

Border cell migration in the Drosophila ovary serves as an in vivo model for the identification of molecular mechanisms that drive collective cell migration. While much is known concerning the physical, mechanical, and adhesive factors that steer the border cells and the cytoskeletal determinants of their morphology, less is known about the mechanisms that govern their initial delamination from the follicular epithelium and the coordination of individual cell polarization, morphology, and behavior. Here we report the identification of a gene, cactin, that is essential for these features of border cell migration. Cactin is conserved in evolution from yeast to man, yet has been ascribed to different biochemical activities in various cells, tissues, and organisms. We show that it is cactin’s conserved spliceosome function that is required in border cells, rather than its reported effects on the Dorsal inhibitor Cactus, or its effect on Rac-mediated actin dynamics. Whole transcriptome analysis shows widespread alterations in splicing, and surprisingly, transcription read-through. Viability and cell fate specification were normal in Cactin knockdown cells, which exhibited individual cell mobility. However, Cactin knockdown caused specific defects in generating a dominant lead cell protrusion and in cluster cohesion. As a result, the cells frequently failed to delaminate. Apical polarity complex proteins were more tightly concentrated in each individual cell, and lost from apical cell-cell junctions and protrusions. These results elucidate a requirement for the spliceosome complex in preventing transcription readthrough and show cell-type-specific defects caused by depletion of a general splicing factor.