NK4 Antagonizes Tbx1/10 to Promote Cardiac versus Pharyngeal Muscle Fate in the Ascidian Second Heart Field

Wei Wang, Florian Razy-Krajka, Eric Siu, Alexandra Ketcham, Lionel Christiaen

Research output: Contribution to journalArticle

Abstract

The heart and head muscles share common developmental origins and genetic underpinnings in vertebrates, including humans. Parts of the heart and cranio-facial musculature derive from common mesodermal progenitors that express NKX2-5, ISL1, and TBX1. This ontogenetic kinship is dramatically reflected in the DiGeorge/Cardio-Velo-Facial syndrome (DGS/CVFS), where mutations of TBX1 cause malformations in the pharyngeal apparatus and cardiac outflow tract. Cardiac progenitors of the first heart field (FHF) do not require TBX1 and segregate precociously from common progenitors of the second heart field (SHF) and pharyngeal muscles. However, the cellular and molecular mechanisms that govern heart versus pharyngeal muscle specification within this lineage remain elusive. Here, we harness the simplicity of the ascidian larva to show that, following asymmetric cell division of common progenitors, NK4/NKX2-5 promotes GATAa/GATA4/5/6 expression and cardiac specification in the second heart precursors by antagonizing Tbx1/10-mediated inhibition of GATAa and activation of Collier/Olf/EBF (COE), the determinant of atrial siphon muscle (ASM) specification. Our results uncover essential regulatory connections between the conserved cardio-pharyngeal factor Tbx1/10 and muscle determinant COE, as well as a mutual antagonism between NK4 and Tbx1/10 activities upstream of GATAa and COE. The latter cross-antagonism underlies a fundamental heart versus pharyngeal muscle fate choice that occurs in a conserved lineage of cardio-pharyngeal progenitors. We propose that this basic ontogenetic motif underlies cardiac and pharyngeal muscle development and evolution in chordates.

Original languageEnglish (US)
Article numbere1001725
JournalPLoS Biology
Volume11
Issue number12
DOIs
StatePublished - Dec 2013

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Pharyngeal Muscles
Urochordata
Ascidiacea
Muscle
heart
muscles
Myocardium
Asymmetric Cell Division
Specifications
Chordata
DiGeorge Syndrome
Muscles
Muscle Development
Siphons
harness
Larva
Vertebrates
muscle development
kinship
Head

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

NK4 Antagonizes Tbx1/10 to Promote Cardiac versus Pharyngeal Muscle Fate in the Ascidian Second Heart Field. / Wang, Wei; Razy-Krajka, Florian; Siu, Eric; Ketcham, Alexandra; Christiaen, Lionel.

In: PLoS Biology, Vol. 11, No. 12, e1001725, 12.2013.

Research output: Contribution to journalArticle

Wang, Wei ; Razy-Krajka, Florian ; Siu, Eric ; Ketcham, Alexandra ; Christiaen, Lionel. / NK4 Antagonizes Tbx1/10 to Promote Cardiac versus Pharyngeal Muscle Fate in the Ascidian Second Heart Field. In: PLoS Biology. 2013 ; Vol. 11, No. 12.
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