Les facteurs à homéodomaine Pitx et Irx au cours du développement des membres postérieurs
The Pitx transcription factors have been implicated in growth and specification of hindlimb identity. First, Pitx1 gene inactivation in mice results in partial transformation of hindlimbs into forelimbs. Further, Pitx1 and Pitx2 have redundant activity for hindlimb growth as demonstrated in double mutant mice for Pitx1 and Pitx2. Indeed, Pitx1-/-;Pitx2neo/neo mice show loss of proximal (femur) and anterior (ilium, tibia and first digit) skeletal structures. A collaborator, Dr C. C. Hui of Toronto University, has demonstrated the importance of the Iroquois (Irx) family transcription factors in hindlimb development. Irx3-/-;Irx5-/- mice show loss of proximal and anterior skeletal structures, exclusively in hindlimbs, even if Irx are expressed in the two limb pairs. This phenocopy between Pitx and Irx mutants led us to investigate the interaction between these transcription factors with three hypotheses : (1) Pitx control Irx expression in hindlimb buds ; (2) the Irx direct Pitx gene expression in hindlimb bud ; (3) Pitx and Irx participate together in a growth regulation cascade in hindlimb buds. Our analyses led us to conclude that Pitx and Irx are in independant genetic cascade in hindlimb buds. However, we observed that Pitx and Irx transcription factors are capable of transcriptionnal interactions assessed using either a generic promoter or conserved regions of the Tbx4 locus. Finally, inactivation of either Pitx or Irx led to a delay of Pax9 expression exclusively in hindlimb buds. In sum, Pitx and Irx gene appear to act on parallel genetic programs involved in control of hindlimbs growth and patterning.
Patterning Transcription Limb growth Limb identity Patterning Gene regulation Transcription Genetic interactions Skeletal development