Genetic Analysis of Distributive Pairing

Stowers Institute For Medical Research, Kansas City MO

Investigators

Abstract

The ordered movement of chromosomes during meiotic cell division is essential to the final development of the organism. In most instances, meiosis is comprised of three basic cellular processes: pairing, recombination and segregation. Pairing identifies homologs, recombination acts to lock them together, and segregation moves them to opposite poles at the first meiotic division. Establishing stable co-orientation requires a balancing of plateward and poleward forces acting on the kinetochores. This balancing of forces is usually achieved by chiasmata, the physical consequence of recombination. However, many organisms also possess systems that ensure the segregation of chromosomes that do not undergo recombination and the Drosophila female is one such organism. The focus of this project is an analysis of the mechanisms that allow proper meiotic segregation in the absence of chromosome exchange. NOD protein has been shown to control the poleward movement of achiasmate homologs as the meiotic spindle elongates during prometaphase. Preliminary data suggests that NOD has two additional functions: 1) providing a plateward balancing force that facilitates proper centromere coorientation; and 2) interlocking homologous chromosomes during early prometaphase. It has also recently been learned that NOD appears to be regulated extra-cellularly during meiotic prometaphase, perhaps via a cAMP-dependent signal transduction system. The specific aims of this project are: 1) Dissect the structure and regulation of the NOD protein. 2) Continue studies of the Axs-transmembrane protein and its possible role in regulating the NOD protein. 3) Genetically test the hypothesis that Nod plays a role in mediating centromere coordination. Failures in achiasmate segregation account for a high fraction of spontaneous nondisjunction in fly and human oocytes. The observation that the protein(s) responsible for achiasmate segregation may be regulated by hormonal cues provides the first insight as to why achiasmate nondisjunction may increase with advancing maternal age in human oocytes.