ERK activation dynamics in maturing oocyte controls embryonic nuclear divisions in Caenorhabditis elegans

Han Bit Baek; Debabrata Das; Shin-Yu Chen; Hongyuan Li; Swathi Arur

doi:10.1016/j.celrep.2024.115157

ERK activation dynamics in maturing oocyte controls embryonic nuclear divisions in Caenorhabditis elegans

Cell Rep. 2025 Jan 9;44(1):115157. doi: 10.1016/j.celrep.2024.115157. Online ahead of print.

Authors

Han Bit Baek¹, Debabrata Das², Shin-Yu Chen², Hongyuan Li², Swathi Arur³

Affiliations

¹ Genetics and Epigenetics Program, University of Texas MD Anderson Cancer Center and The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA; Department of Genetics, University of Texas MD Anderson Cancer Center and The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA.
² Department of Genetics, University of Texas MD Anderson Cancer Center and The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA.
³ Genetics and Epigenetics Program, University of Texas MD Anderson Cancer Center and The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA; Department of Genetics, University of Texas MD Anderson Cancer Center and The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA. Electronic address: [email protected].

PMID: 39792558
DOI: 10.1016/j.celrep.2024.115157

Abstract

ERK activity oscillates between sustained activation during oocyte formation and transient inactivation during oocyte maturation, fertilization, and early embryogenesis. Consequences of ectopic ERK activity upon oocyte maturation and in early embryogenesis are unknown. We show, in Caenorhabditis elegans, that ectopic ERK activity upon oocyte maturation (metaphase I oocytes) results in embryos with abnormalities in nuclear divisions leading to embryonic death. We uncover that ERK directly phosphorylates Polo-like kinase I (PLK-1), on Serine 404, to inhibit nuclear envelope breakdown (NEBD) in early embryogenesis. The RAS/ERK/PLK-1 pathway poisons zygotic NEBD and inhibits the merging of parental genomes, underlining the importance of turning off ERK prior to embryogenesis. Given the conserved nature of both ERK signaling to oocyte development and PLK1 to embryonic divisions, this work has implications for women undergoing in vitro fertilization (IVF) where ectopic ERK activation during superovulation through hormonal stimulation may diminish oocyte quality and influence zygotic development.

Keywords: C. elegans; CP: Cell biology; CP: Developmental biology; ERK signaling; NEBD; PLK-1; RASopathies; early embryo; meiosis I; oocyte fertilization; oocyte maturation; oocyte-to-embryo transition.