| Date and Time: |
2007-11-19 16:00:00 - 17:00:00 |
| Speaker: |
Frank Conlon
Department of Genetics, University of North Carolina |
| Title: |
Molecular Pathways of Cardiac Progenitor Proliferation and Survival |
| Summary : | The isolation and culturing of cardiac progenitor cells has demonstrated that growth factor signaling is required to maintain cardiac cell survival and proliferation. In this study, we demonstrate that SHP-2 activity is required for the maintenance of cardiac precursors in vivo. In the absence of SHP-2 signaling, cardiac progenitor cells down-regulate genes associated with early heart development and fail to initiate cardiac differentiation. We further show that this requirement for SHP-2 is restricted to cardiac precursor cells undergoing active proliferation. By demonstrating that SHP-2 is phosphorylated on Y542/Y580 and that it binds to FRS-2, we place SHP-2 in the FGF pathway during early embryonic heart development. Furthermore, we demonstrate that inhibition of FGF signaling mimics the cellular and biochemical effects of SHP-2 inhibition and that these effects can be rescued by constitutively active/Noonan syndrome associated forms of SHP-2. Collectively, these results show that SHP-2 functions within the FGF/MAPK pathway to maintain survival of proliferating populations of cardiac progenitor cells. A screen to identify the molecular pathways functioning downstream of FGF/SHP-2 in the developing heart has identified additional components of the SHP-2 pathway and is suggestive of a role for SHP-2 in cell polarity and cell cycle control. |
