Flower (Drosophila)
Flower is a transmembrane protein family in Drosophila whose isoforms mark cells as fit or unfit for survival.
Function
The flower gene produces multiple splice isoforms with opposite signaling meanings. The isoforms Flower^LoseA and Flower^LoseB appear on cells destined to die and serve as “eat-me” signals: neighboring cells and hemocytes recognize them and eliminate the displaying cell. The isoform Flower^Win appears on cells that outcompete their neighbors. The system implements cell competition at the molecular level: in a tissue where some cells grow slower than others - through Myc deficiency, mitochondrial defects, or mutation - the slow cells display Flower^Lose and are killed and phagocytosed by their faster neighbors, even though they are healthy in isolation. The winner cells actively kill the losers; the losers’ death requires the winners’ Flower signal.
Cell competition
Flower is the best-characterized molecular marker of cell competition, the phenomenon that connects multicellular cooperation to cancer: the same comparison mechanism that removes defective cells from a tissue will, in a tumor, remove the fitter normal cells in favor of the fitter clone. Cell competition is one of the somatic dynamics that tempers complete de-Darwinization of tissues. Mammalian homologs (Frem1-family proteins, and the flower isoform system in mice) have been identified with comparable lose/win isoform structure, and Flower isoforms are expressed in human cancer, where the lose isoform correlates with apoptosis and the win isoform with tumor progression.
Notes
- Drosophila gene: flower (fwe); mammalian homologs: Fwe/Frem-family isoforms.
- Discovered in Drosophila developmental cell competition; isoform logic conserved in mice.