Uncovering mechanisms controlling chromosome-specific behaviors during meiosis

Project Summary Meiosis is a tightly controlled process during which the diploid genome must segregate into haploid gametes (i.e. eggs or sperm). Inheritance of the incorrect number of chromosomes causes fertility and birth defects. However, the causes of chromosome missegregation are not always conserved between chromosomes and the reasons for inter-chromosomal differences are still unknown. One key contributor appears to be either a complete loss of crossing over or abnormal crossover placement. Drosophila melanogaster is a powerful model to better elucidate the regulation of chromosome- specific crossing over and the effects on chromosome segregation. In most cases, mutants that disrupt crossing over do so uniformly across the genome making it difficult to understand how chromosome-specific defects occur. However, a recently identified set of mutants in a partial loss-of- function synaptonemal complex mutant exhibit substantially different defects in pairing and recombination on the X chromosome and the autosomes. The synaptonemal complex is a conserved meiotic structure that holds homologous chromosomes together and is necessary for crossing over to occur. The long- term goal of this project is to investigate how the synaptonemal complex regulates chromosome- specific recombination and meiotic behaviors necessary for segregation. This work will investigate 1) the role of the synaptonemal complex in regulating the recombination landscape and 2) the importance of chromosome structure informing meiotic behaviors. Furthermore, this project will establish a new toolkit for analyzing individual chromosomes. Overall, this project will provide insights into both the regulation of crossover location and meiotic chromosome biology. By studying the importance of individual chromosome behaviors and the synaptonemal complex in recombination, substantial advances can be made in understand the biology underlying the development of aneuploidies.