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First published online 10 October 2007
doi: 10.1242/dev.009290

Development 134, 4119-4130 (2007)
Published by The Company of Biologists 2007
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SHP-2 is required for the maintenance of cardiac progenitors

Yvette G. Langdon1,2,*, Sarah C. Goetz1,2,*, Anna E. Berg2, Jackie Thomas Swanik1,2,3 and Frank L. Conlon1,2,3,{dagger}

1 Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, NC 27599, USA.
2 Department of Biology, Fordham Hall, University of North Carolina, Chapel Hill, NC 27599, USA.
3 Department of Genetics, Fordham Hall, University of North Carolina, Chapel Hill, NC 27599, USA.

{dagger} Author for correspondence (e-mail: frank_conlon{at}med.unc.edu)

Accepted 31 August 2007

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 in Xenopus that SHP-2 activity is required for the maintenance of cardiac precursors in vivo. In the absence of SHP-2 signaling, cardiac progenitor cells downregulate 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.

Key words: SHP-2, Cardiac, Xenopus, Cell cycle, Survival, FGF






© The Company of Biologists Ltd 2007