ArticlePLoS biology2013
NK4 antagonizes Tbx1/10 to promote cardiac versus pharyngeal muscle fate in the ascidian second heart field.
Article in PLoS biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 84 citations in OpenAlex.
- Multi-stage single-cell atlas of a chordate non-embryonic development unveils dedifferentiating bud founder cells.Nature communications · 2026Article
- Cell numbers contribute to cell fate during Ciona cardiopharyngeal mesoderm specification.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cell cycle-driven transcriptome maturation confers multilineage competence to cardiopharyngeal progenitors.The EMBO journal · 2025Article
- Nkx2.7 is a conserved regulator of craniofacial development.Nature communications · 2025Article
- Cellular remodeling and JAK inhibition promote zygotic gene expression in the Ciona germline.EMBO reports · 2024Article
- Cardiac Progenitor Cells of the First and Second Heart Fields.Advances in experimental medicine and biology · 2024Article
- The second heart field: the first 20 years.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Ring Finger 149-Related Is an FGF/MAPK-Independent Regulator of Pharyngeal Muscle Fate Specification.International journal of molecular sciences · 2023Article
- Lateral thinking in syndromic congenital cardiovascular disease.Disease models & mechanisms · 2023Article
- Overview of Head Muscles with Special Emphasis on Extraocular Muscle Development.Advances in anatomy, embryology, and cell biology · 2023Article
- Comparing dormancy in two distantly related tunicates reveals morphological, molecular, and ecological convergences and repeated co-option.Scientific reports · 2022Article
- The Emergence of Embryonic Myosin Heavy Chain during Branchiomeric Muscle Development.Life (Basel, Switzerland) · 2022Article
- GATA4/5/6 family transcription factors are conserved determinants of cardiac versus pharyngeal mesoderm fate.Science advances · 2022Article
- Article
- The ontology of the anatomy and development of the solitary ascidian Ciona: the swimming larva and its metamorphosis.Scientific reports · 2020Article
- Article
- A single-cell transcriptional roadmap for cardiopharyngeal fate diversification.Nature cell biology · 2019Article
- HDAC1-mediated repression of the retinoic acid-responsive gene ripply3 promotes second heart field development.PLoS genetics · 2019Article
- Initial characterization of Wnt-Tcf functions during Ciona heart development.Developmental biology · 2019Article
- Nr2f-dependent allocation of ventricular cardiomyocyte and pharyngeal muscle progenitors.PLoS genetics · 2019Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
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.
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