Deciphering how signals between cells coordinate heart development is essential for the diagnosis and treatment of congenital heart disorders. Our long-term goal is to gain a comprehensive understanding of how one of these signals, fibroblast growth factor (FGF) impacts early heart formation. The complexity of this process in vertebrate embryos has hindered progress. We have begun to exploit the simplicity of Ciona intestinalis, a close evolutionary relative of the vertebrates, to investigate a conserved role for FGF in early heart development. Our specific hypothesis is that a broad FGF signal is refined by limiting downstream activation of the Ets transcription factor. This hypothesis is based on the observations that;1) heart specification in Ciona requires Ets activity downstream of FGF signaling;2) Ets expression is limited to four founder cells;and 3) FGF drives asymmetric division/specification within the Ets expressing founder cell lineage. First, we will decipher Ets transcriptional regulation. Next, we will assess the potential roles of an FGF gradient or differential competence in restricting heart specification within the Ets expressing founder cells. Completion of the proposed studies will provide substantial insights into the transcriptional and cellular responses to FGF signaling during heart development.

Public Health Relevance

. Defects in heart development are pervasive, occurring in 1-2% of newborn infants. The complexity of cell signaling during initial heart formation has hindered progress in understanding the genetic causes of these defects. We propose to use the simple embryos of the sea squirt, Ciona intestinalis to better understand conserved cell signaling events critical to proper heart formation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL091027-05
Application #
8277922
Study Section
Cardiovascular Differentiation and Development Study Section (CDD)
Program Officer
Schramm, Charlene A
Project Start
2008-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2012
Total Cost
$280,103
Indirect Cost
$57,353
Name
Swarthmore College
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
073755381
City
Swarthmore
State
PA
Country
United States
Zip Code
19081
Norton, Jennifer; Cooley, James; Islam, A F M Tariqul et al. (2013) Matrix adhesion polarizes heart progenitor induction in the invertebrate chordate Ciona intestinalis. Development 140:1301-11
Cooley, James; Whitaker, Stacia; Sweeney, Sarah et al. (2011) Cytoskeletal polarity mediates localized induction of the heart progenitor lineage. Nat Cell Biol 13:952-7
Ragkousi, Katerina; Beh, Jeni; Sweeney, Sarah et al. (2011) A single GATA factor plays discrete, lineage specific roles in ascidian heart development. Dev Biol 352:154-63