A novel small molecule that disrupts a key event during the oocyte-to-embryo transition in C. elegans

Steven E. Weicksel, Assaf Mahadav, Mark Moyle, Patricia G. Cipriani, Michelle Kudron, Zachary Pincus, Shirin Bahmanyar, Laura Abriola, Janie Merkel, Michelle Gutwein, Anita G. Fernandez, Fabio Piano, Kristin C. Gunsalus, Valerie Reinke

Research output: Contribution to journalArticlepeer-review

Abstract

The complex cellular events that occur in response to fertilization are essential for mediating the oocyte-to-embryo transition. Here, we describe a comprehensive small-molecule screen focused on identifying compounds that affect early embryonic events in Caenorhabditis elegans. We identify a single novel compound that disrupts early embryogenesis with remarkable stage and species specificity. The compound, named C22, primarily impairs eggshell integrity, leading to osmotic sensitivity and embryonic lethality. The C22-induced phenotype is dependent upon the upregulation of the LET-607/CREBH transcription factor and its candidate target genes, which primarily encode factors involved in diverse aspects of protein trafficking. Together, our data suggest that in the presence of C22, one or more key components of the eggshell are inappropriately processed, leading to permeable, inviable embryos. The remarkable specificity and reversibility of this compound will facilitate further investigation into the role and regulation of protein trafficking in the early embryo, as well as serve as a tool for manipulating the life cycle for other studies such as those involving aging.

Original languageEnglish (US)
Pages (from-to)3540-3548
Number of pages9
JournalDevelopment (Cambridge)
Volume143
Issue number19
DOIs
StatePublished - Oct 1 2016

Keywords

  • C. elegans
  • Oocyte-to-embryo transition
  • Secretory pathway
  • Small molecule

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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