1. Academic Validation
  2. Activation of P53 pathway contributes to Xenopus hybrid inviability

Activation of P53 pathway contributes to Xenopus hybrid inviability

  • Proc Natl Acad Sci U S A. 2023 May 23;120(21):e2303698120. doi: 10.1073/pnas.2303698120.
Zhaoying Shi 1 Guanghui Liu 1 Hao Jiang 1 Songyuan Shi 1 Xuan Zhang 1 Yi Deng 1 Yonglong Chen 1
Affiliations

Affiliation

  • 1 Department of Chemical Biology, School of Life Sciences, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, 518055 Shenzhen, China.
Abstract

Hybrid incompatibility as a kind of reproductive isolation contributes to speciation. The nucleocytoplasmic incompatibility between Xenopus tropicalis eggs and Xenopus laevis sperm (te×ls) leads to specific loss of paternal chromosomes 3L and 4L. The hybrids die before gastrulation, of which the lethal causes remain largely unclear. Here, we show that the activation of the tumor suppressor protein P53 at late blastula stage contributes to this early lethality. We find that in stage 9 embryos, P53-binding motif is the most enriched one in the up-regulated Assay for Transposase-Accessible Chromatin with high-throughput Sequencing (ATAC-seq) peaks between te×ls and wild-type X. tropicalis controls, which correlates with an abrupt stabilization of P53 protein in te×ls hybrids at stage 9. Inhibition of P53 activity via either tp53 knockout or overexpression of a dominant-negative P53 mutant or Murine double minute 2 proto-oncogene (MDM2), a negative regulator of P53, by mRNA injection can rescue the te×ls early lethality. Our results suggest a causal function of P53 on hybrid lethality prior to gastrulation.

Keywords

P53; Xenopus; hybrid inviability; reproductive isolation.

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