title: The T-box transcription factor Tbx15 is required for skeletal development.
abstract: During early limb development several signaling centers coordinate limb bud outgrowth as well as patterning. Members of the T-box gene family of transcriptional regulators are crucial players in these processes by activating and interpreting these signaling pathways. Here, we show that Tbx15, a member of this gene family, is expressed during limb development, first in the mesenchyme of the early limb bud, then during early endochondral bone development in prehypertrophic chondrocytes of cartilaginous templates. Expression is also found in mesenchymal precursor cells and prehypertrophic chondrocytes, respectively, during development of skeletal elements of the vertebral column and the head. Analysis of Tbx15 null mutant mice indicates a role of Tbx15 in the development of skeletal elements throughout the body. Mutants display a general reduction of bone size and changes of bone shape. In the forelimb skeleton, the scapula lacks the central region of the blade. Cartilaginous templates are already reduced in size and show a transient delay in ossification in mutant embryos. Mutants show a significantly reduced proliferation of prehypertrophic chondrocytes as well as of mesenchymal precursor cells. These data suggest that Tbx15 plays an important role in the development of the skeleton of the limb, vertebral column and head by controlling the number of mesenchymal precursor cells and chondrocytes.
authors.affiliation: Institut für Molekularbiologie, OE5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Manvendra K
authors.initials: MK
authors.lastname: Singh
authors.forename: Marianne
authors.initials: M
authors.lastname: Petry
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Haenig
authors.forename: Birgit
authors.initials: B
authors.lastname: Lescher
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.forename: Andreas
authors.initials: A
authors.lastname: Kispert
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D019521:Body Patterning; D001846:Bone Development; D001842:Bone and Bones / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism; D017931:DNA Primers / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D005121:Extremities / Q000196:embryology*; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009154:Mutation; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000096:biosynthesis* / Q000502:physiology*; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D020825:T-Box Domain Proteins; C114093:TBX15 protein, mouse