Fibroblast Growth Factor (FGF) and downstream Mitogen Activated Protein Kinase (MapK) signaling play important roles during early cardiac fate specification and throughout cardiac development. In the Davidson lab we use the model chordate, Ciona intestinalis, to explore early signaling events required for heart progenitor fate specification. In Ciona embryos, FGF/MapK signaling differentially activates the Ets1/2 transcription factor in heart progenitor cells up-regulating the expression of a number of cardiogenic genes, including the transcription factors, FoxF, Hand-like and GATAa. Previous work from our lab has shown that interaction with a localized extrinsic cue is required to mediate FGF/MapK activation cardiac founder cells. What mediates this interaction and how it acts to modulate FGF/MapK activation, and hence, induction in cardiac founder cells remains unclear. I will test the hypothesis: Matrix adhesion influences heart progenitor induction by modulating FGF receptor (FGFR) trafficking. This hypothesis is based on three observations. 1) Focal matrix adhesions co-localize with regions of FGF/MapK induction. 2) Targeted inactivation of matrix adhesion disrupts heart progenitor induction. 3) Targeted expression of integrin beta 2 restores disrupted matrix adhesion and heart progenitor induction. To test this hypothesis I will pursue the following aims: Aim 1: Identify the integrin receptor beta subunits that contribute to heart progenitor induction. Aim 2: Identify the integrin receptor alpha subunits that contribute to heart progenitor induction. Aim 3: Determine whether integrin receptor activity influences heart progenitor induction by modulating FGFR trafficking.
|Program type||Postdoctoral Fellowship|
|Effective start/end date||01/01/2013 → 12/31/2014|