University of Minnesota
University of Minnesota
College of Biological Sciences

David Greenstein, PhD

PhD: Rockefeller University, 1989


Research Techniques:

Genetics, RNAi, Microscopy, Biochemistry, Cell Biology


Research Interests:

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.


Selected Publications:

Kim, S., Spike, C., & Greenstein D. (2013). “Control of oocyte growth and meiotic maturation in C. elegans.” C. elegans germline development (T. Schedl, ed.), in: Advances in experimental medicine and biology (Springer, New York) 757: 277-320.
Ernstrom, G. G., Weimer R., Pawar, D. R., Watanabe, S., Hobson, R. J., Greenstein, D., & Jorgensen, E. M. (2012). “V-ATPase V1 sector is required for corpse clearance and neurotransmission in Caenorhabditis elegans.” Genetics 191: 461-475.

Kim, S., Govindan, J. A., Tu, Z. J., & Greenstein, D. (2012). “The SACY-1 DEAD-box helicase links the somatic control of oocyte meiotic maturation to the sperm-to-oocyte switch and gamete maintenance in Caenorhabditis elegans.” Genetics in press.

Nadarajan, S., Govindan, J. A., McGovern, M., Hubbard, E. J., & Greenstein, D. (2009).“MSP and GLP-1/Notch signaling coordinately regulate actomyosine-dependent cytoplasmic streaming and oocyte growth in C. elegans.” Development 136: 2223-2234.

Govindan, J. A., Nadarajan, S., Kim, S., Starich, T. A., & Greenstein, D. (2009). “Somatic cAMP signaling regulates MSP-dependent oocyte growth and meiotic maturation in C. elegans.” Development 136: 2211-2221.

Cheng, H., Govindan, J. A., & Greenstein, D.  (2008).  "Regulated trafficking of the MSP/Eph receptor during oocyte meiotic maturation in C. elegans."  Current Biology, *18*, 705-714.

Harris, J. E., Govindan, J. A., Yamamoto, I., Schwartz, J., Kaverina, I., & Greenstein, D.  (2006).  “The major sperm protein signals the reorganization of oocyte microtubles prior to fertilization in Caenorhabditis elegans.”  Developmental Biology, 299, 105-121.

Govindan, J. A., Cheng, H., Harris, J. E., & Greenstein, D.  (2006).  “Gao/i and Gas signaling function in parallel with the MSP/Eph receptor to control meiotic diapause in C. elegans.  Current Biology 16, 1257-1268.

Yamamoto, I., Kosinski, M. E., & Greenstein, D.  (2006).  “Start me up:  Cell signaling and the journey from oocyte to embryo in C. elegans.”  Developmental Dynamics 235, 571-585.

Greenstein, D., & Lee, L. A.  (2006).  “Oogenesis-to-embryogenesis transition:  kinase cabal plots regime change.”  Current Biology 16, R93-R95.

Kosinski, M., McDonald, K., Schwartz, J., Yamamoto, I., & Greenstein, D.  (2005).  “C. elegans sperm bud vesicles to deliver a meiotic maturation signal to distant oocytes.”  Development 132, 3357-3369.

Greenstein, D.  (2005).  “Control of oocyte meiotic maturation and fertilization.”  (December 28, 2005), WormBook, ed.  The C. elegans Research Community,WormBook, doi/10.1895/wormbook.1.53.1,

Hubbard, E. J., & Greenstein, D.  “Introduction to the germline.”  (September 1, 2005), WormBook, ed.  The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.18.1,

Miller, M. A., Cutter, A., Yamamoto, I., Ward, S., & Greenstein, D. (2004).  “Clustered organization of reproductive genes in the C. elegans genome.”  Current Biology 14:  1284-1290.

Miller, M. A., Ruest, P. J., Kosinski, M., Hanks, S. K., & Greenstein, D.  (2003).  “An Eph receptor sperm-sensing control mechanism for oocyte meiotic maturation in Caenorhabditis elegans.”  Genes & Development 17:  187-200.

Miller, M. A., Nguyen, V. Q., Lee, M.-H., Kosinski, M., Schedl., T., Caprioli, R. M., & Greenstein, D.  (2001).  “A sperm cytoskletal protein that signals oocyte meiotic maturation and ovulation.”  Science 291: 2144-2147.

Rutledge, E., Bianchi, L., Christensen, M., Boehmer, C., Morrison, R., Broslat, A., Beld, A., George Jr., A. L., Greenstein, D., & Strange, K.  (2001).  “A ClC-2 anion channel ortholog activated during meiotic maturation in C. elegans oocytes.” Current Biology 11, 161-170.

Furuta, T., Tuck, S., Kirchner, J., Koch, B., Auty, R., Kitagawa, R., Rose, A. M. & Greenstein, D.  (2000).  “EMB-30:  an APC4 homolog required for metaphase to anaphase transitions during meiosis and mitosis in Caenorhabditis elegans.”  Mol. Biol. Cell 11:  1401-1419.

Hubbard, E. J. A. & Greenstein, D.  (2000).  “The C. elegans gonad:  a test tube for cell and developmental biology.”  Developmental  Dynamics 218:  2-22.

Hall, D. H., Winfrey, V. P., Blaeuer, G., Hoffman, L. H., Furuta, T., Rose, K. L., O. Hobert & Greenstein, D.  (1999).  “Ultrastructural features of the adult hermaphrodite gonad of Caenorhabditis elegans:  relations between the germ line and soma.”  Developmental Biology 212:  101-123.

Rose K. L., Winfrey, V. P., Hoffman, L. H., Hall, D. H., Furuta, T. & Greenstein, D.  (1997).  “The POU-gene ceh-18 promotes gonadal sheath cell differentiation and function required for meiotic maturation and ovulation in Caenorhabditis elegans.” Developmental Biology 192, 59-77.

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