title: A novel small molecule that disrupts a key event during the oocyte-to-embryo transition in C. elegans.
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.
authors: Dept. of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Steven E
authors: SE
authors: Weicksel
authors: Dept. of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA Center for Genomics and Systems Biology, Dept. of Biology, New York University, New York, NY 10003, USA.
authors: Assaf
authors: A
authors: Mahadav
authors: Dept. of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Mark
authors: M
authors: Moyle
authors: Center for Genomics and Systems Biology, Dept. of Biology, New York University, New York, NY 10003, USA.
authors: Patricia G
authors: PG
authors: Cipriani
authors: Dept. of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Michelle
authors: M
authors: Kudron
authors: Dept. of Developmental Biology and Dept. of Genetics, Washington University in St Louis, St Louis, MO 63110, USA.
authors: Zachary
authors: Z
authors: Pincus
authors: Dept. of Molecular Cell and Developmental Biology, Yale University, New Haven, CT 06520, USA.
authors: Shirin
authors: S
authors: Bahmanyar
authors: Yale Center for Molecular Discovery, West Haven, CT 06516, USA.
authors: Laura
authors: L
authors: Abriola
authors: Yale Center for Molecular Discovery, West Haven, CT 06516, USA.
authors: Janie
authors: J
authors: Merkel
authors: Center for Genomics and Systems Biology, Dept. of Biology, New York University, New York, NY 10003, USA.
authors: Michelle
authors: M
authors: Gutwein
authors: Dept. of Biology, Fairfield University, Fairfield, CT 06824, USA.
authors: Anita G
authors: AG
authors: Fernandez
authors: Center for Genomics and Systems Biology, Dept. of Biology, New York University, New York, NY 10003, USA Division of Biological Sciences, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates fp1@nyu.edu kcg1@nyu.edu valerie.reinke@yale.edu.
authors: Fabio
authors: F
authors: Piano
authors: Center for Genomics and Systems Biology, Dept. of Biology, New York University, New York, NY 10003, USA Division of Biological Sciences, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates fp1@nyu.edu kcg1@nyu.edu valerie.reinke@yale.edu.
authors: Kristin C
authors: KC
authors: Gunsalus
authors: Dept. of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA fp1@nyu.edu kcg1@nyu.edu valerie.reinke@yale.edu.
authors: Valerie
authors: 0000-0002-8967-2756
authors: V
authors: Reinke
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D014157:Transcription Factors
keywords: C. elegans; Oocyte-to-embryo transition; Secretory pathway; Small molecule