C.elegans Heredity and Development

We want to understand the mechanisms insuring uniparental and maternal inheritance of the mitochondrial genome and the associated stakes.

Oocyte fertilization by the spermatozoon is a critical step of sexual reproduction that triggers massive and quick modifications in the egg. Genetic and epigenetic contributions are not identical from both gametes, the mitochondrial DNA being transmitted from the oocyte only. This uniparental and maternal inheritance is a conserved property among a large proportion of animal species. The maternal inheritance of the mitochondrial genome is responsible for the maternal transmission of several mitochondrial human diseases and the mechanisms of paternal mitochondrial genome exclusion and/or degradation remain largely unclear.

We identified the autophagy as the main mechanism of this elimination using C. elegans embryo and are now focusing on :

  • The identification of the targeting signal.
  • Understanding the consequences of their stabilization for the embryo development and for the subsequent progenies.

We also use this simple and powerful experimental system to study the autophagy mechanism itself.

More...

We want to understand the mechanisms insuring uniparental and maternal inheritance of the mitochondrial genome and the associated stakes.

Oocyte fertilization by the spermatozoon is a critical step of sexual reproduction that triggers massive and quick modifications in the egg. Genetic and epigenetic contributions are not identical from both gametes, the mitochondrial DNA being transmitted from the oocyte only. This uniparental and maternal inheritance is a conserved property among a large proportion of animal species. The maternal inheritance of the mitochondrial genome is responsible for the maternal transmission of several mitochondrial human diseases but the mechanisms of paternal mitochondrial genome exclusion and/or degradation remain largely unclear. We identified the autophagy as the main mechanism of this elimination using C. elegans as a system model. Autophagy is an intracellular degradation process involving the incorporation of proteins aggregates or whole organelles in a double membrane compartment that eventually fuses with acidic lysosomal compartments to trigger the degradation and recycling of the cargos.

Highlights

We demonstrated that sperm organelles enter the embryo upon fertilization and trigger the formation au autophagosomes visualized by the recruitment of the two C. elegans homologues of the yeast ATG8p protein: LGG-1 and LGG-2 (Al Rawi et al., Science 2012). These two proteins are ubiquitin like proteins are ubiquitin like proteins that are coupled to a lipid anchor and associate with autophagosomal membrane during their formation and maturation. They are collectively essential for autophagy and contribute to sperm-inherited component degradation and therefore to the uniparental and maternal inheritance of the mitochondrial genome. We contributed to understand their respective contributions in the process. Using live imaging of newly fertilized C. elegans embryos we demonstrated that LGG-2 contributes to the acidification of the autophagosomes by controlling their spatial distribution within the embryo (Djeddi et al., Development 2015). It is essential for their pericentrosomal localization and to facilitate their fusion with the lysosomal compartments. 

Future directions

We are now focusing on :

  • The identification of the targeting signal that allows the specific removal of the paternal mitochondria while they are surrounded by a large amount of oocyte-derived mitochondria.
  • Understanding the consequences of their stabilization for the embryo development and for the subsequent progenies.
  • We also use this simple and powerful experimental system to study the autophagy mechanism itself.

Collaborations

  • Thomas Boudier, IBPS, UPMC, Paris - France
  • Renaud Legouis, CNRS CGM, Gif sur Yvette - France
  • Martin Sachse, PFMU, Institut Pasteur, Paris - France
  • Jean-Yves Tinevez, PFID, Institut Pasteur, Paris - France