title: Development of a subset of forelimb muscles and their attachment sites requires the ulnar-mammary syndrome gene Tbx3.
abstract: In the vertebrate limb over 40 muscles are arranged in a precise pattern of attachment via muscle connective tissue and tendon to bone and provide an extensive range of motion. How the development of somite-derived muscle is coordinated with the development of lateral plate-derived muscle connective tissue, tendon and bone to assemble a functional limb musculoskeletal system is a long-standing question. Mutations in the T-box transcription factor, TBX3, have previously been identified as the genetic cause of ulnar-mammary syndrome (UMS), characterized by distinctive defects in posterior forelimb bones. Using conditional mutagenesis in mice, we now show that TBX3 has a broader role in limb musculoskeletal development. TBX3 is not only required for development of posterior forelimb bones (ulna and digits 4 and 5), but also for a subset of posterior muscles (lateral triceps and brachialis) and their bone eminence attachment sites. TBX3 specification of origin and insertion sites appears to be tightly linked with whether these particular muscles develop and may represent a newly discovered mechanism for specification of anatomical muscles. Re-examination of an individual with UMS reveals similar previously unrecognized muscle and bone eminence defects and indicates a conserved role for TBX3 in regulating musculoskeletal development.
authors.affiliation: Department of Human Genetics, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Colasanto
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel.
authors.forename: Shai
authors.initials: S
authors.lastname: Eyal
authors.affiliation: Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institutes of Health, Building 35, Room 2A-116, MSC 3705, 35 Convent Drive, Bethesda, MD 20892-3705, USA.
authors.forename: Payam
authors.initials: P
authors.lastname: Mohassel
authors.affiliation: University of Washington School of Medicine, Department of Pediatrics, Division of Genetic Medicine, 1959 NE Pacific Street HSB I-607-F, Seattle, WA 98195-7371, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bamshad
authors.affiliation: Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institutes of Health, Building 35, Room 2A-116, MSC 3705, 35 Convent Drive, Bethesda, MD 20892-3705, USA.
authors.forename: Carsten G
authors.initials: CG
authors.lastname: Bonnemann
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel.
authors.forename: Elazar
authors.initials: E
authors.lastname: Zelzer
authors.affiliation: Weis Center for Research, Geisinger Clinic, 100 North Academy Avenue, Danville, PA 17822, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Moon
authors.affiliation: Department of Human Genetics, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA gkardon@genetics.utah.edu.
authors.forename: Gabrielle
authors.identifier: 0000-0003-2144-4463
authors.initials: G
authors.lastname: Kardon
mesh_terms: D000015:Abnormalities, Multiple / Q000473:pathology*; D000818:Animals; D001941:Breast Diseases / Q000473:pathology*; D019070:Cell Lineage; D005260:Female; D005552:Forelimb / Q000473:pathology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009132:Muscles / Q000473:pathology*; D056740:Olecranon Process / Q000473:pathology; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D013710:Tendons / Q000473:pathology; D014457:Ulna / Q000002:abnormalities* / Q000473:pathology
chemical_list: D020825:T-Box Domain Proteins; C491460:Tbx3 protein, mouse
keywords: Bone; Limb; Muscle; Tbx3; UMS; Ulnar-mammary syndrome