FGF signaling delineates the cardiac progenitor field in the simple chordate, Ciona intestinalis

Abstract

Comprehensive gene networks in Ciona intestinalis embryos provide a foundation for characterizing complex developmental processes, such as the initial phases of chordate heart development. The basic helix–loop–helix regulatory gene Ci-Mesp is required for activation of cardiac transcription factors. Evidence is presented that Ci-Ets1/2, a transcriptional effector of receptor tyrosine kinase (RTK) signaling, acts downstream from Mesp to establish the heart field. Asymmetric activation of Ets1/2, possibly through localized expression of FGF9, drives heart specification within this field. During gastrulation, Ets1/2 is expressed in a group of four cells descended from two Mesp-expressing founder cells (the B7.5 cells). After gastrulation, these cells divide asymmetrically; the smaller rostral daughters exhibit RTK activation (phosphorylation of ERK) and form the heart lineage while the larger caudal daughters form the anterior tail muscle lineage. Inhibition of RTK signaling prevents heart specification. Targeted inhibition of Ets1/2 activity or FGF receptor function also blocks heart specification. Conversely, application of FGF or targeted expression of constitutively active Ets1/2 (EtsVp16) cause both rostral and caudal B7.5 lineages to form heart cells. This expansion produces an unexpected phenotype: transformation of a single-compartment heart into a functional multicompartment organ. We discuss these results with regard to the development and evolution of the multichambered vertebrate heart.