Regulation and evolution of cardiopharyngeal cell identity and behavior: insights from simple chordates

Abstract

The vertebrate heart arises from distinct first and second heart fields. The latter also share a common origin with branchiomeric muscles in the pharyngeal mesoderm and transcription regulators, such as Nkx2–5, Tbx1 and Islet1. Despite significant progress, the complexity of vertebrate embryos has hindered the identification of multipotent cardiopharyngeal progenitors. Here, we summarize recent insights in cardiopharyngeal development gained from ascidian models, among the closest relatives to vertebrates. In a simplified cellular context, progressive fate specification of the ascidian cardiopharyngeal precursors presents striking similarities with their vertebrate counterparts. Multipotent cardiopharyngeal progenitors are primed to activate both the early cardiac and pharyngeal muscles programs, which segregate following asymmetric cells divisions as a result of regulatory cross-antagonisms involving Tbx1 and Nkx2–5 homologs. Activation of Ebf in pharyngeal muscle founder cells triggers both Myogenic Regulatory Factor-associated differentiation and Notch-mediated maintenance of an undifferentiated state in distinct precursors. Cross-species comparisons revealed the deep conservation of the cardiopharyngeal developmental sequence in spite of extreme genome sequence divergence, gene network rewiring and specific morphogenetic differences. Finally, analyses are beginning to uncover the influence of surrounding tissues in determining cardiopharyngeal cell identity and behavior. Thus, ascidian embryos offer a unique opportunity to study gene regulation and cell behaviors at the cellular level throughout cardiopharyngeal morphogenesis and evolution.

Rewiring of an ancestral Tbx1/10-Ebf-Mrf network for pharyngeal muscle specification in distinct embryonic lineages

“…In mice, Tbx1 regulates Myf5 and MyoD in the myogenic branchial arch mesoderm (Sambasivan et al, 2009), and is required for formation of striated esophageal muscles, both of which derive from Mesp1+ cardiopharyngeal mesoderm (Gopalakrishnan et al, 2015). Indeed, it has been proposed that the Mesp+ B7.5 lineage is homologous to the vertebrate cardiopharyngeal mesoderm (Stolfi et al, 2010;Wang et al, 2013;Kaplan et al, 2015;Diogo et al, 2015). By contrast, we show that Tbx1/10 has no role in activating or maintaining Ebf expression in the OSM lineage (Fig.…”

Evaluation and rational design of guide RNAs for efficient CRISPR/Cas9-mediated mutagenesis in Ciona

“…The majority of these genes are transcription factors and signaling molecules of potential interest in the study of cardiopharyngeal mesoderm development. The cardiopharyngeal mesoderm of Ciona , also known as the Trunk Ventral Cells (TVCs), are multipotent cells that invariantly give rise to the heart and pharyngeal muscles of the adult (Hirano and Nishida 1997; Stolfi et al 2010; Razy-Krajka et al 2014), thus sharing a common ontogenetic motif with the cardiopharyngeal mesoderm of vertebrates (Wang et al 2013b; Diogo et al 2015; Kaplan et al 2015). …”

Combinatorial chromatin dynamics foster accurate cardiopharyngeal fate choices

“…Moreover, these analyses are partially hindered by the complexity of early vertebrate embryos. By contrast, the tunicate Ciona emerged as a simple and powerful chordate model to study early cardiopharyngeal development at high spatio-temporal resolution 8,12 ( Fig. 1A).…”