title: Pitx1 is necessary for normal initiation of hindlimb outgrowth through regulation of Tbx4 expression and shapes hindlimb morphologies via targeted growth control.
abstract: The forelimbs and hindlimbs of vertebrates are morphologically distinct. Pitx1, expressed in the hindlimb bud mesenchyme, is required for the formation of hindlimb characteristics and produces hindlimb-like morphologies when misexpressed in forelimbs. Pitx1 is also necessary for normal expression of Tbx4, a transcription factor required for normal hindlimb development. Despite the importance of this protein in these processes, little is known about its mechanism of action. Using a transgenic gene replacement strategy in a Pitx1 mutant mouse, we have uncoupled two discrete functions of Pitx1. We show that, firstly, this protein influences hindlimb outgrowth by regulating Tbx4 expression levels and that, subsequently, it shapes hindlimb bone and soft tissue morphology independently of Tbx4. We provide the first description of how Pitx1 sculpts the forming hindlimb skeleton by localised modulation of the growth rate of discrete elements.
authors: Division of Developmental Biology, MRC-National Institute for Medical Research, The Ridgeway, London, UK.
authors: Veronique
authors: V
authors: Duboc
authors: Malcolm P O
authors: MP
authors: Logan
mesh_terms: D000818:Animals; D019521:Body Patterning; D001846:Bone Development; D018507:Gene Expression Regulation, Developmental; D006614:Hindlimb / Q000254:growth & development* / Q000378:metabolism; D008648:Mesoderm / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000378:metabolism*
chemical_list: D051761:Paired Box Transcription Factors; D020825:T-Box Domain Proteins; C103177:Tbx4 protein, mouse; C101485:homeobox protein PITX1