Fibroblast Growth Factor (FGF) signaling is critical for many steps in the formation of the heart including induction and proliferation of cardiac progenitor cells. In the invertebrate chordate, Ciona intestinalis, matrix adhesion is required to polarize the response of cardiac founder cells to extrinsic FGF and promote differential heart progenitor induction. With the support of the AHA we have identified ci-IntB2 and ci-IntA2 as the specific integrin receptor subunits necessary for adhesion-mediated heart progenitor induction. However, the precise mechanism by which adhesion polarizes inductive signaling has remained unclear. I will test the hypothesis: Matrix adhesion modulates membrane stability to facilitate regional retention of Fibroblast Growth Factor Receptors (FGFRs) and promote differential heart progenitor induction. This hypothesis is based on three observations: 1) Targeted disruption of matrix adhesion disrupts heart progenitor induction. 2) FGFRs concentrate within adhesive membrane domains, thereby promoting differential inductive signaling 3) Matrix adhesion inhibits internalization and degradation of FGFRs. To test this hypothesis I will pursue the following aims: Aim 1 will identify the precise mechanism by which IntB2; restores FGF-mediated heart progenitor induction. Aim 2 will identify the precise mechanism by which IntA2; restores FGF-mediated heart progenitor induction.
|Program type||Postdoctoral Fellowship|
|Effective start/end date||01/01/2016 → 12/31/2016|