Meeting Abstract
Matrix adhesion is intimately linked to developmental signaling and fate induction. Precise cellular mechanisms impacting inductive signaling downstream of adhesion, such as the contribution of cytoskeletal activity, remain unclear. The cellular and genetic simplicity of our model organism, Ciona intestinalis, allows us to study in vivo cellular processes driving early heart specification events. We have shown that heart progenitor induction requires Fibroblast Growth Factor (FGF) signaling and involves polarized distribution of FGF receptors (FGFR). Polarized receptor distribution is aided by adhesion and membrane-stabilizing Caveolin-rich domains. We have also demonstrated that cytoskeletal protrusive activity coordinates a differential response to uniform FGF. However, the precise mechanism underlying localized retention of FGFRs in the heart progenitor cells remains poorly understood. Here we investigate the potential contribution of a cytoskeletal protein, Filamin (FLN). FLN modulates Caveolin trafficking downstream of matrix adhesion and may thereby stabilize FGFR. To test this hypothesis, we expressed a dominant-negative form of FLN in the heart lineage. Targeted disruption of FLN function caused increased induction, indicating that FLN destabilizes FGFR by promoting internalization and membrane turnover. We are therefore investigating the effect of FLN disruption on receptor distribution. Future studies disrupting specific binding domains of FLN may elucidate the functional interaction responsible for increased induction. Our work has the potential to unravel the role of cytoskeleton in coordinating a localized response to uniform inductive signals.
