Cell Surface Changes During the Egg-to-Embryo Transition

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PROJECT¿SUMMARY¿ ¿ 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¿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.¿¿ ¿ PROJECT¿NARRATIVE¿ ¿ 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.¿