title: HEART DEVELOPMENT. Integration of Bmp and Wnt signaling by Hopx specifies commitment of cardiomyoblasts.
abstract: Cardiac progenitor cells are multipotent and give rise to cardiac endothelium, smooth muscle, and cardiomyocytes. Here, we define and characterize the cardiomyoblast intermediate that is committed to the cardiomyocyte fate, and we characterize the niche signals that regulate commitment. Cardiomyoblasts express Hopx, which functions to coordinate local Bmp signals to inhibit the Wnt pathway, thus promoting cardiomyogenesis. Hopx integrates Bmp and Wnt signaling by physically interacting with activated Smads and repressing Wnt genes. The identification of the committed cardiomyoblast that retains proliferative potential will inform cardiac regenerative therapeutics. In addition, Bmp signals characterize adult stem cell niches in other tissues where Hopx-mediated inhibition of Wnt is likely to contribute to stem cell quiescence and to explain the role of Hopx as a tumor suppressor.
authors.affiliation: Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Rajan
authors.initials: R
authors.lastname: Jain
authors.affiliation: Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Mudit
authors.initials: M
authors.lastname: Gupta
authors.affiliation: Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Manderfield
authors.affiliation: Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Ifkovits
authors.affiliation: Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Qiaohong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Feiyan
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Andrey
authors.initials: A
authors.lastname: Poleshko
authors.affiliation: Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Arun
authors.initials: A
authors.lastname: Padmanabhan
authors.affiliation: Department of Genetics, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Raum
authors.affiliation: Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Edward E
authors.initials: EE
authors.lastname: Morrisey
authors.affiliation: Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Min Min
authors.initials: MM
authors.lastname: Lu
authors.affiliation: Department of Genetics, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kyoung-Jae
authors.initials: KJ
authors.lastname: Won
authors.affiliation: Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. epsteinj@upenn.edu.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Epstein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage / Q000235:genetics; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D032386:Myoblasts, Cardiac / Q000166:cytology / Q000378:metabolism*; D038081:Organogenesis / Q000235:genetics*; D055153:Stem Cell Niche / Q000235:genetics / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics*
chemical_list: D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; C466740:Hop protein, mouse; D025521:Tumor Suppressor Proteins