The meiotic entry network

Meiosis is a specialized cell division, which is essential for the generation of haploid germ cells. Reduction of the chromosome content in meiosis is necessary to compensate for the doubling of chromosome numbers after fertilization. Meiosis also contributes to genetic diversity by reciprocal exchanges of paternal and maternal chromosomes. Defects in meiotic cell divisions are the leading cause of miscarriages and diseases linked to mental retardation. At meiosis onset, the two chromosome sets of the father and the mother need to find each other and undergo a physical linkeage, which ensures their subequent accurate segregation into two daughter cells. At the same time, genetic material is exchanged between parental chromosomes. The events leading to this physical likeage need to be tightly regulated and coordinated. In a previous project we could show that loss of this coordination leads to missing links between homologous parental chromosomes, followed by chomosome mis-segregation, which leads to the generation of inviable offspring. With this proposal we suggest to study the regulatory events that ensure proper meiotic entry and progression. This will be achieved by using a mutant defective in meiotic progression and an isolated suppressor mutant, recently isolated in our lab. We use the genetic model system Caenorhabditis elegans, which allows us to combine biochemistry with genetics and cell biology. At the same time, the genes and factors involved in the regulation of meiosis are also found in mammalian systems therefore allowing to transfer the knowledge gained in our study to higher organisms including humans. Ultimately this project will contribute to a better understanding of genetic risk factors for compromised fertility and birth defects due to chromosomal mal-segregation.

Meiosis is a specialized cell division, which is essential for the generation of haploid germ cells. Reduction of the chromosome content in meiosis is necessary to compensate for the doubling of chromosome numbers after fertilization. Meiosis also contributes to genetic diversity by reciprocal exchanges of paternal and maternal chromosomes. Defects in meiotic cell divisions are the leading cause of miscarriages and diseases linked to mental retardation. At meiosis onset, the two chromosome sets of the father and the mother need to find each other and undergo a physical linkeage, which ensures their subequent accurate segregation into two daughter cells. At the same time, genetic material is exchanged between parental chromosomes. The events leading to this physical likeage need to be tightly regulated and coordinated. In a previous project we could show that loss of this coordination leads to missing links between homologous parental chromosomes, followed by chomosome mis-segregation, which leads to the generation of inviable offspring. With this proposal we identified and characterized the phosphatase PPM-1.D/Wip1 as inportant player in the regulatory events that ensure proper meiotic entry and progression.