PARENT SESSION
MINISYMPOSIUM XII. Cell Interactions and Growth Factors in Oocyte-Somatic Cell Communication.
11:00 AM-12:30 PM
Grand Ballroom VI
Chair: Schomberg, David¹, ¹

(M35) CELLULOMICS OF COMMUNICATION IN THE DEVELOPING OVARIAN FOLLICLE.

Albertini, David¹, ¹ Dept. of Anatomy and Cellular Biology, Boston, MA

ABSTRACT- An integrated understanding of ovarian follicular development is being achieved by the combined approaches of genomics, proteomics and cellulomics. Cellulomics attempts to integrate two dimensional informatics (gene/transcript, protein/protein) into the realm of cellular behaviors that encompass functional matrices. Matrices have been modeled for a variety of cellular behaviors that include the generation of cell polarity, cell cycle control, transcriptional control, and cell migration and adhesion. This presentation will focus on cellulomic principles revealed by the analysis of ovarian follicular phenotypes that result from the targeted deletion of "communication" genes in mice. The impact of disrupted communication between the oocyte and granulosa cells, using these models and phenotype rescue strategies where possible, reveals stage specific coupling defects in the processes of folliculogenesis and oogenesis. Paracrine factors mediate a dialogue between oocytes and granulosa during preantral follicle development. When the oocyte-derived TFG- GDF-9 is eliminated, follicular development but not oogenesis, is interrupted indicating discordance in suppression of oocyte growth and development when appropriate GDF-9 target cells fail to respond. Failure to orient granulosa cells to establish contact with the oocyte may underlie this discordance in coordinated development. Gap junctions mediate various aspects of direct intercellular communication between somatic and germ cell compartments of the follicle and gene expression patterns appear to be developmentally regulated. Connexin 37 knockout mice display arrest of oogenesis in mid growth phase and a failure to support folliculogenesis at the antral transition despite the availability of FSH and FSH receptors on granulosa cells. This suggests gap junction communication based signaling from the oocyte activates a cell cycle checkpoint whose passage is instrumental in the development of the oocyte. Thus, discordancies parallel in this situation resulting in tandem developmental arrest. Finally, FSH- null animals reveal a novel discordance in oogenesis and folliculogenbesis that maps to the regulation of genes involved in the establishment and maintenance of cell polarity. The "epithelialization" of the granulosa during preantral follicle growth is shown to involve repositioning of the granulosa cell centrosome to the zona-apposed/apical border. FSH induces cytoskeletal remodeling in granulosa cells such that centrosome and Golgi are relocated away from the oocyte, possibly to facilitate delivery of oocyte-derived factors to somatic follicular cells. The spatial integration of communication pathways within the follicle therefore derive from positional cues at the oocyte-granulosa interface and illustrate how cellulomics synergize with genomic and proteomic determinants in ovarian development.

KEY WORDS: follicle, paracrine signalling, oocyte, cell communication