title: Genetics of shoulder girdle formation: roles of Tbx15 and aristaless-like genes.
abstract: The diverse cellular contributions to the skeletal elements of the vertebrate shoulder and pelvic girdles during embryonic development complicate the study of their patterning. Research in avian embryos has recently clarified part of the embryological basis of shoulder formation. Although dermomyotomal cells provide the progenitors of the scapular blade, local signals appear to have an essential guiding role in this process. These signals differ from those that are known to pattern the more distal appendicular skeleton. We have studied the impact of Tbx15, Gli3, Alx4 and related genes on formation of the skeletal elements of the mouse shoulder and pelvic girdles. We observed severe reduction of the scapula in double and triple mutants of these genes. Analyses of a range of complex genotypes revealed aspects of their genetic relationship, as well as functions that had been previously masked due to functional redundancy. Tbx15 and Gli3 appear to have synergistic functions in formation of the scapular blade. Scapular truncation in triple mutants of Tbx15, Alx4 and Cart1 indicates essential functions for Alx4 and Cart1 in the anterior part of the scapula, as opposed to Gli3 function being linked to the posterior part. Especially in Alx4/Cart1 mutants, the expression of markers such as Pax1, Pax3 and Scleraxis is altered prior to stages when anatomical aberrations are visible in the shoulder region. This suggests a disorganization of the proximal limb bud and adjacent flank mesoderm, and is likely to reflect the disruption of a mechanism providing positional cues to guide progenitor cells to their destination in the pectoral girdle.
authors.affiliation: Hubrecht Laboratory, The Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: Kuijper
authors.forename: Annemiek
authors.initials: A
authors.lastname: Beverdam
authors.forename: Carla
authors.initials: C
authors.lastname: Kroon
authors.forename: Antje
authors.initials: A
authors.lastname: Brouwer
authors.forename: Sophie
authors.initials: S
authors.lastname: Candille
authors.forename: Gregory
authors.initials: G
authors.lastname: Barsh
authors.forename: Frits
authors.initials: F
authors.lastname: Meijlink
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities* / Q000196:embryology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012782:Shoulder / Q000196:embryology*; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000074290:Zinc Finger Protein Gli3
chemical_list: C489986:Alx1 protein, mouse; C113607:Alx3 protein, mouse; C109218:Alx4 protein, mouse; D004268:DNA-Binding Proteins; C465571:Gli3 protein, mouse; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; C491060:Phox2a protein, mouse; D020825:T-Box Domain Proteins; C114093:TBX15 protein, mouse; D014157:Transcription Factors; D000074290:Zinc Finger Protein Gli3