If fertilized, all eggs undergo an egg-to-embryo transition. Within minutes or hours of insemination, depending on the animal, the egg shuffles its existing molecular machinery and transforms itself into a cell with vastly different developmental potential. The first mechanistic alteration of this egg-to-embryo transition establishes the block to polyspermy, which is followed by and integrated with the turnover of maternal mRNA and cytoplasmic proteins, altered signal transduction capabilities, and changes at the cell surface including the addition and removal of specific membrane proteins and lipids. This transition is independent of new transcriptional activity, and for technical reasons, a majority of recent research towards understanding the egg-to-embryo transition has focused on signal transduction mechanisms and changes in mRNAs. The sea urchin and starfish, however, offer an opportunity to examine the changes that occur specifically at the cell surface. While the details of this process differ among animals, as with much of the reproductive phenomena, all eggs undergo this general transition. We will take advantage of the sea urchin and starfish because 1) millions of oocytes, eggs and embryos are readily obtained;2) all the major proteins of the cortical granules have been defined;3) the egg and oocyte plasma membrane can be manipulated experimentally in many ways;and 4) the genome sequence and genomic resources from the sea urchin Strongylocentrotus purpuratus are available. Results of this study will elucidate conserved mechanisms of this major developmental transition in all animals. Furthermore, because the changes examined here are at the cell surface, they will help clinicians develop new methods to non-invasively assess developmental potential in IVF applications for humans.

Public Health Relevance

Immediately after fertilization, the egg rapidly transforms into an embryo with many new biochemical, cellular, and developmental features. This essential change is programmed into the egg and is independent of new gene expression;i.e., they reflect changes of the existing molecular machinery. Our research focuses on the changes that occur on the cell surface of the egg to embryo transition. These are some of the most rapid and conserved changes that occur in embryos and are detectable from the outside of the cell. Thus, this research will lead to a better understanding of a major transition in fertilization and development of all animals, and to the identification of non invasive, early markers indicative of successful development. Our results will have particular significance to clinical IVF predictions in human reproductive health.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD028152-15
Application #
7595737
Study Section
Cellular, Molecular and Integrative Reproduction Study Section (CMIR)
Program Officer
Moss, Stuart B
Project Start
1991-05-01
Project End
2012-03-31
Budget Start
2009-04-01
Budget End
2010-03-31
Support Year
15
Fiscal Year
2009
Total Cost
$253,822
Indirect Cost
Name
Brown University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Fresques, Tara M; Wessel, Gary M (2018) Nodal induces sequential restriction of germ cell factors during primordial germ cell specification. Development 145:
Schudrowitz, Natalie; Takagi, Satoshi; Wessel, Gary M et al. (2017) Germline factor DDX4 functions in blood-derived cancer cell phenotypes. Cancer Sci 108:1612-1619
Oulhen, Nathalie; Swartz, S Zachary; Laird, Jessica et al. (2017) Transient translational quiescence in primordial germ cells. Development 144:1201-1210
Shevidi, Saba; Uchida, Alicia; Schudrowitz, Natalie et al. (2017) Single nucleotide editing without DNA cleavage using CRISPR/Cas9-deaminase in the sea urchin embryo. Dev Dyn 246:1036-1046
Brayboy, Lynae M; Oulhen, Nathalie; Long, Sokunvichet et al. (2017) Multidrug resistance transporter-1 and breast cancer resistance protein protect against ovarian toxicity, and are essential in ovarian physiology. Reprod Toxicol 69:121-131
Oulhen, Nathalie; Wessel, Gary M (2016) Differential Nanos 2 protein stability results in selective germ cell accumulation in the sea urchin. Dev Biol 418:146-156
Fresques, Tara; Swartz, Steven Zachary; Juliano, Celina et al. (2016) The diversity of nanos expression in echinoderm embryos supports different mechanisms in germ cell specification. Evol Dev 18:267-78
Brayboy, L M; Wessel, G M (2016) The double-edged sword of the mammalian oocyte--advantages, drawbacks and approaches for basic and clinical analysis at the single cell level. Mol Hum Reprod 22:200-7
Oulhen, Nathalie; Heyland, Andreas; Carrier, Tyler J et al. (2016) Regeneration in bipinnaria larvae of the bat star Patiria miniata induces rapid and broad new gene expression. Mech Dev 142:10-21
Oulhen, Nathalie; Wessel, Gary M (2016) Albinism as a visual, in vivo guide for CRISPR/Cas9 functionality in the sea urchin embryo. Mol Reprod Dev 83:1046-1047

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