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Presenting Author(s) Emilie Dumontier;
Jean-François Ouimette
Abstract Title Pitx1and Pitx2 are required for development of hindlimb buds.
Full author List Emilie Dumontier, Jean-François Ouimette, Alexandre Marcil, Michel Chamberland, Sally A. Camper, Jacques Drouin
Text of abstract

Two closely related homeobox transcription factors, Pitx1 and Pitx2, have been implicated in the patterning of lateral plate mesoderm derivatives. Indeed, Pitx1 was identified as the most upstream determinant of hindlimb identity and Pitx2 was shown to be an effector for determination of left/right asymmetry. We show that together Pitx1 and Pitx2 are required for formation of hindlimb buds. We have noted asymmetric development of hindlimbs in embryo mutants for the Pitx1 gene and this led to the hypothesis that the Pitx1 and Pitx2 genes might have partly redundant functions in the control of hindlimb development. In addition to the patterning defects previously associated with the specification function of Pitx1, embryos deficient in Pitx1 and partially deficient in Pitx2 revealed a dose-dependant loss of proximal (femur) and anterior (tibia and digit 1) structures in hindlimbs. We observed a delay in AER-Fgf8 expression and a reduction in the size of early limb buds. While Pitx1 is expressed throughout developing hindlimb buds, Pitx2 is not expressed in limb bud mesenchyme itself. Since the Pitx genes are only co-expressed very early in the hindlimb field before bud outgrowth, it is suggested that Pitx genes are required for the onset and/or maintenance of mesoderm proliferation in the hindlimb field. In normal conditions, this function is primarily provided by Pitx1, but in the absence of Pitx1, Pitx2 partially compensated. Thus, Pitx1 and Pitx2 genes are required for sustained hindlimb bud growth and formation of hindlimbs.

We are also investigating the action of Pitx genes on downstream targets, in particular on Tbx4 gene regulation. Taken together, these studies will define mechanisms of Pitx and Tbx genes action during limb development.

Which session is your work most relevant to: Limb initiation