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 journalArticle

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

Fingerprint

Egg Shell
Oocytes
Embryonic Structures
Protein Transport
Species Specificity
Linear Energy Transfer
Caenorhabditis elegans
Life Cycle Stages
Fertilization
Embryonic Development
Transcription Factors
Up-Regulation
Phenotype
Genes

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Weicksel, S. E., Mahadav, A., Moyle, M., Cipriani, P. G., Kudron, M., Pincus, Z., ... Reinke, V. (2016). A novel small molecule that disrupts a key event during the oocyte-to-embryo transition in C. elegans. Development (Cambridge), 143(19), 3540-3548. https://doi.org/10.1242/dev.140046

A novel small molecule that disrupts a key event during the oocyte-to-embryo transition in C. elegans. / Weicksel, Steven E.; Mahadav, Assaf; Moyle, Mark; Cipriani, Patricia G.; Kudron, Michelle; Pincus, Zachary; Bahmanyar, Shirin; Abriola, Laura; Merkel, Janie; Gutwein, Michelle; Fernandez, Anita G.; Piano, Fabio; Gunsalus, Kristin C.; Reinke, Valerie.

In: Development (Cambridge), Vol. 143, No. 19, 01.10.2016, p. 3540-3548.

Research output: Contribution to journalArticle

Weicksel, SE, Mahadav, A, Moyle, M, Cipriani, PG, Kudron, M, Pincus, Z, Bahmanyar, S, Abriola, L, Merkel, J, Gutwein, M, Fernandez, AG, Piano, F, Gunsalus, KC & Reinke, V 2016, 'A novel small molecule that disrupts a key event during the oocyte-to-embryo transition in C. elegans', Development (Cambridge), vol. 143, no. 19, pp. 3540-3548. https://doi.org/10.1242/dev.140046
Weicksel SE, Mahadav A, Moyle M, Cipriani PG, Kudron M, Pincus Z et al. A novel small molecule that disrupts a key event during the oocyte-to-embryo transition in C. elegans. Development (Cambridge). 2016 Oct 1;143(19):3540-3548. https://doi.org/10.1242/dev.140046
Weicksel, Steven E. ; Mahadav, Assaf ; Moyle, Mark ; Cipriani, Patricia G. ; Kudron, Michelle ; Pincus, Zachary ; Bahmanyar, Shirin ; Abriola, Laura ; Merkel, Janie ; Gutwein, Michelle ; Fernandez, Anita G. ; Piano, Fabio ; Gunsalus, Kristin C. ; Reinke, Valerie. / A novel small molecule that disrupts a key event during the oocyte-to-embryo transition in C. elegans. In: Development (Cambridge). 2016 ; Vol. 143, No. 19. pp. 3540-3548.
@article{6423c7fb64544896a85bf3537947891f,
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.",
keywords = "C. elegans, Oocyte-to-embryo transition, Secretory pathway, Small molecule",
author = "Weicksel, {Steven E.} and Assaf Mahadav and Mark Moyle and Cipriani, {Patricia G.} and Michelle Kudron and Zachary Pincus and Shirin Bahmanyar and Laura Abriola and Janie Merkel and Michelle Gutwein and Fernandez, {Anita G.} and Fabio Piano and Gunsalus, {Kristin C.} and Valerie Reinke",
year = "2016",
month = "10",
day = "1",
doi = "10.1242/dev.140046",
language = "English (US)",
volume = "143",
pages = "3540--3548",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "19",

}

TY - JOUR

T1 - A novel small molecule that disrupts a key event during the oocyte-to-embryo transition in C. elegans

AU - Weicksel, Steven E.

AU - Mahadav, Assaf

AU - Moyle, Mark

AU - Cipriani, Patricia G.

AU - Kudron, Michelle

AU - Pincus, Zachary

AU - Bahmanyar, Shirin

AU - Abriola, Laura

AU - Merkel, Janie

AU - Gutwein, Michelle

AU - Fernandez, Anita G.

AU - Piano, Fabio

AU - Gunsalus, Kristin C.

AU - Reinke, Valerie

PY - 2016/10/1

Y1 - 2016/10/1

N2 - 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.

AB - 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.

KW - C. elegans

KW - Oocyte-to-embryo transition

KW - Secretory pathway

KW - Small molecule

UR - http://www.scopus.com/inward/record.url?scp=84991387569&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991387569&partnerID=8YFLogxK

U2 - 10.1242/dev.140046

DO - 10.1242/dev.140046

M3 - Article

VL - 143

SP - 3540

EP - 3548

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 19

ER -