David Greenstein

Meiosis and fertilization are fundamental and fascinating developmental events, yet they remain incompletely understood despite a century of study. In most sexually reproducing animals, oocytes arrest in meiotic prophase and resume meiosis (meiotic maturation) in response to sperm or somatic cell signals. Proper chromosome segregation during meiosis is critical for the viability of the fertilized egg. In humans, dysregulation of the meiotic process is a major cause of miscarriage, infertility, and Down Syndrome. In many species, hormones trigger signal transduction cascades that regulate meiosis and promote oocyte meiotic maturation and ovulation. Short-range contact-dependent signals between oocytes and somatic cells of the gonad also regulate meiotic maturation. Hormonal dysfunction in humans may play a role in the etiology of meiotic defects because their frequency is increased in both pregnancies of women over forty and early adolescent pregnancies.

To complement studies in vertebrates, the Greenstein lab is using the nematode Caenorhaditis elegans as a model for studying the control of meiosis by intercellular signaling. Sexual reproduction relies on reciprocal soma-germline interactions, in addition to complex interactions between gametes. Our studies demonstrate that the C. elegans major sperm protein (MSP), a cytoskeletal protein required for amoeboid motility of nematode sperm, has a second critical function as a hormone that promotes oocyte meiotic maturation, ovulation, and fertilization. The MSP signal acts on both oocytes and the somatic gonad, culminating in the activation of conserved signaling cascades that promote M-phase entry, cytoskeletal reorganization, meiotic spindle assembly, and fertilization. Ongoing research is aimed at elucidating the molecular mechanisms underlying these key developmental events using a combination of molecular genetics, genomics, biochemistry, and cell biology.