Molecular Genetics of Development - CNRS URA2578  


  HEADProf. BUCKINGHAM Margaret / margab@pasteur.fr
  MEMBERSBAJARD Lola / Dr BAJOLLE Fanny / Dr CRIST Colin / Dr DAUBAS Philippe / Dr ESNER Milan
Dr GALLI Daniela / LAGHA Mounia / Dr MEILHAC Sigolène / Dr MONTARRAS Didier
Dr RELAIX Frédéric / Dr SATO Takahiko / Dr VINCENT Stéphane / Dr WATANABE Yusuke


  Annual Report

Our Unit works on myogenesis and cardiogenesis, using the tools of mouse molecular genetics to examine cell behaviour and gene function.

Skeletal myogenesis

Myogenic regulatory factors of the MyoD family are essential for muscle cell determination and differentiation. We are focussing on the upstream signalling pathways and transcriptional regulators that control the activation of these genes, both during skeletal muscle formation in the embryo and regeneration in the adult.

We had established genetically that Pax3 and Pax7 play an essential role in conferring myogenic potential and ensuring the survival of progenitor cells during the development of skeletal muscle. We now show that Pax3 directly activates a regulatory element of the myogenic determination gene, Myf5, at the onset of myogenesis in the limbs and in some trunk muscles. We have shown that the same progenitor cell that gives rise to skeletal muscle can also form smooth muscle after down-regulation of Pax3.

We recently demonstrated that muscle satellite cells efficiently repair damaged skeletal muscle. In Pax7 mutant mice, these cells are depleted. We now show that this is due to progressive cell death. Pax3 does not compensate for this antiapoptotic function of Pax7, postnatally. Both Pax3 and Pax7 can activate MyoD expression in satellite cells. In the absence of Myf5, this is essential for their entry into the myogenic programme.

Current work on myogenesis includes the identification of Pax3/7 co-activators and targets, and examination of other regulators, such as Blimp1.

Cardiogenesis

Research on cardiogenesis centers on our demonstration that two cell lineages contribute to the myocardium, and that there is a second heart field, characterized by a distinct gene regulatory network.

The cardiac outflow tract is formed entirely from the second lineage. We have now identified sub-populations of progenitor cells, in the anterior part of the second heart field that contribute different domains of outflow tract myocardium. Markers of these subdomains reveal rotation of the outflow tract, which underlies the correct alignment of the great arteries. This has implications for congenital heart disease.

Current work on the second heart field includes analysis of the role of Fgf signalling, the contribution of this field to the atria and the segregation of myocardial lineages at gastrulation.

buckingham.jpg

Les embryons transgéniques avec un gène rapporteur nlacZ sous contrôle d’une séquence régulatrice à -58/-57 kb du gène Myf5 (A) ou cette même séquence avec le site Pax3 muté (B).

Transgenic embryos in which an nlacZ reporter is controlled by a -58/-57 kb Myf5 regulatory sequence (A) or this sequence with the Pax3 site mutated (B).



  Web Site

More informations on our web site


  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
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