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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Cardiovascular Differentiation and Development Study Section (CDD)
Program Officer
Schramm, Charlene A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Arizona
Schools of Arts and Sciences
United States
Zip Code
Palmquist, Karl; Davidson, Brad (2017) Establishment of lateral organ asymmetries in the invertebrate chordate, Ciona intestinalis. Evodevo 8:12
Segade, Fernando; Cota, Christina; Famiglietti, Amber et al. (2016) Fibronectin contributes to notochord intercalation in the invertebrate chordate, Ciona intestinalis. Evodevo 7:21
Cota, Christina D; Davidson, Brad (2015) Mitotic Membrane Turnover Coordinates Differential Induction of the Heart Progenitor Lineage. Dev Cell 34:505-19
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
Woznica, Arielle; Haeussler, Maximilian; Starobinska, Ella et al. (2012) Initial deployment of the cardiogenic gene regulatory network in the basal chordate, Ciona intestinalis. Dev Biol 368:127-39
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
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