Journal
DEVELOPMENT
Volume 138, Issue 24, Pages 5301-5309Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.074153
Keywords
Pitx1; Limb-type morphology; Tbx4; Mouse
Categories
Funding
- European Molecular Biology Organisation long-term fellowship
- Marie Curie Actions Intra European Fellowship for career development
- Medical Research Council
- Medical Research Council [MC_U117560477] Funding Source: researchfish
- MRC [MC_U117560477] Funding Source: UKRI
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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.
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