Nuclear Lamina Remodeling in Meiosis

Meiosis is a specialized cell division program, 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. Active meiotic chromosome movements are a universally conserved feature. They occur at the early stages of prophase of the first meiotic division and support the ordered side by side alignment of the chromosomes of the two parents, which is a prerequisite for the success of the ensuing genetic exchange, which is triggered by programmed DNA double strand break induction. Chromosome movements are driven by forces in the cytoplasm, which are passed on to chromosome ends attached to the nuclear periphery by nuclear-membrane-spanning protein modules. In animals, the nuclear lamina forms a rigid proteinaceous network that underlies the inner nuclear membrane to provide stability to the nucleus. With this propsal we want to examine how the nuclear lamina has to be modified to not pose an obstacle to the chromosome end-led movement process. For our analysis we use the genetic model system Caenorhabditis elegans and we combine biochemical analysis with genetics and cell biology. With this we will be able to establish a framework to understand nuclear lamina remodelling in meiosis to address this question in higher vertebrates. Next to nothing is known of lamina behaviour in vertebrate meiosis.