Nucleoporin37 may play a role in early embryo development in human and mice

Mol Hum Reprod. 2022 May 27;28(6):gaac017. doi: 10.1093/molehr/gaac017.

Abstract

Maternal-effect genes (MEGs) play an important role in maintaining the survival and development of mammalian embryos at the cleavage stage after fertilization. Despite long-term efforts, the MEGs that regulate preimplantation embryo development remain largely unknown. Here, using whole-exome sequencing and homozygosity mapping, we identified a potential candidate gene associated with early embryo development: nucleoporin37 (NUP37), a nucleoporin gene that encodes a member of the nuclear pore complexes and regulates nuclear pore permeability and nucleocytoplasmic transport. Moreover, we determined the temporal and spatial expression patterns of Nup37 in mouse oocytes and early embryos, and explored the role of NUP37 in oocyte maturation and preimplantation embryo development. Immunoprecipitation assays confirmed that yes-associated protein-1 (YAP1) binds to TEA domain transcription factor 4 (TEAD4) and NUP37. Furthermore, Nup37 gene knockdown reduced the nuclear import of YAP1 and down-regulated the expression of YAP1-TEAD pathway downstream genes Rrm2 and Rpl13 in early embryos. Our study provides evidence that maternal NUP37 contributes to the nuclear import of YAP1 and then activates the YAP1-TEAD pathway, a signalling pathway essential for zygotic genome activation. Nup37 may be a key gene involved in preimplantation embryo development in mammals.

Keywords: MEGs; NUP37; YAP1–TEAD pathway; ZGA; early embryo development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • Embryo, Mammalian / metabolism
  • Embryonic Development* / genetics
  • Gene Expression Regulation, Developmental
  • Humans
  • Mammals / genetics
  • Mice
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Neoplasm Proteins / genetics
  • Oocytes / metabolism
  • Oogenesis
  • Ribosomal Proteins / genetics
  • TEA Domain Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zygote*

Substances

  • DNA-Binding Proteins
  • Muscle Proteins
  • Neoplasm Proteins
  • RPL13 protein, human
  • Ribosomal Proteins
  • TEA Domain Transcription Factors
  • TEAD4 protein, human
  • Transcription Factors