Heart genetics in a small package, exploiting the condensed genome of Ciona intestinalis

Abstract

Defects in the initial establishment of cardiogenic cell fate are likely to contribute to pervasive human congenital cardiac abnormalities. However, the molecular underpinnings of nascent cardiac fate induction have proven difficult to decipher. In this review we explore the participation of extracellular, cellular and nuclear factors in comprehensive specification networks. At each level, we elaborate on insights gained through the study of cardiogenesis in the invertebrate chordate Ciona intestinalis and propose productive lines of future research. In-depth discussion of pre-cardiac induction is intended to serve as a paradigm, illustrating the potential use of Ciona to elucidate comprehensive networks underlying additional aspects of chordate cardiogenesis, including directed migration and subspecification of cardiac and pharyngeal lineages.

Keywords: FGF; Mesp; cardiac induction; chordate evolution; extracellular matrix; gene regulatory networks.

Figure 1:

Nascent chordate cardiac progenitor specification superimposed on Waddington’s epigenetic landscape (modified from previous studies [1, 2]). (A) Mesp establishes the transcriptional state underlying pre-cardiac competence. Subsequent ETS-mediated shifts in transcription further restrict cardiopharyngeal progenitor cell fate. (B) Proximal transcription and chromatin remodeling factors (red) directly shape the cardiac gene regulatory landscape. Distal extracellular cues (green) and signal transduction complexes (blue) can modify these transcriptional networks. (C) FGF-mediated cardiac induction in Ciona. Asymmetric division of pre-cardiac cells (solid yellow) gives rise to cardiopharyngeal (orange striped) and skeletal muscle (purple dots) progenitors. After induction, cardiopharyngeal progenitors migrate rostrally (gray arrows) into the head–trunk region of the tailbud embryo.

Figure 2:

Schematic depiction of inputs regulating Ciona cardiac induction. Red lines indicate transcriptional inputs, blue lines indicate cellular signaling inputs and green lines indicate extracellular inputs.