214C Poster - 01. Cell Stress and cell death
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Frank Macabenta; Hsuan-Te Sun; Angelike Stathopoulos

Affiliation: California Institute of Technology, Pasadena, CA

Keywords:
b. death mutants/genes; x. homeostasis

Organ integrity requires the elimination of abnormal cells to avoid compromised patterning and function. While cell competition has been characterized as a way to eliminate abnormal cells in epithelial tissues, little is known about how collectively-migrating mesenchymal cells maintain quality control. Here we investigate how lost cells within a migratory cohort are eliminated prior to organogenesis using the Drosophila embryonic caudal visceral mesoderm (CVM), migratory cells that ultimately form the midgut musculature. Through a combination of genetic manipulation, immunostaining, and confocal live imaging, we find that FGF signaling via heartless (htl) is critical to maintaining cell survival by antagonizing the cell death gene head involution defective (hid) specifically in the CVM, and that expression of hid is regulated in a cell-cycle dependent manner prior to myoblast fusion, ensuring that unfit cells are cleared before they can contribute to assembly. We additionally use a cell cycle-coupled degron system to show that precise coordination of the cell cycle is mediated by BMP signaling supported by CVM-expressed Tolkin (Tok) metalloprotease processing secreted Decapentaplegic (Dpp) ligand in the extracellular milieu. Mechanistically, we identified a BMP-responsive enhancer that controls expression of the mitotic activator string (stg) in the visceral mesoderm. Through this study, we have demonstrated a system by which collectively migrating mesenchymal cells can control for migration errors via crosstalk between FGF and BMP signaling, and how errors in this system can result in significant consequences, including inappropriate invasion of other tissues.