Maternal methylosome protein 50 is essential for embryonic development in medaka Oryzias latipes

J Exp Zool A Ecol Integr Physiol. 2024 Apr 23. doi: 10.1002/jez.2824. Online ahead of print.

Abstract

Methylosome protein 50 (Mep50) is a protein that is rich in WD40 domains, which mediate and regulate a variety of physiological processes in organisms. Previous studies indicated the necessity of Mep50 in embryogenesis in mice Mus musculus and fish. This study aimed to further understand the roles of maternal Mep50 in early embryogenesis using medaka Oryzias latipes as a model. Without maternal Mep50, medaka zygotes developed to the pre-early gastrula stage but died later. The transcriptome of the embryos at the pre-early gastrula stage was analyzed by RNA sequencing. The results indicated that 1572 genes were significantly upregulated and 741 genes were significantly downregulated in the embryos without maternal Mep50. In the differentially expressed genes (DEGs), the DNA-binding proteins, such as histones and members of the small chromosome maintenance complex, were enriched. The major interfered regulatory networks in the embryos losing maternal Mep50 included DNA replication and cell cycle regulation, AP-1 transcription factors such as Jun and Fos, the Wnt pathway, RNA processing, and the extracellular matrix. Quantitative RT-PCR verified 16 DEGs, including prmt5, H2A, cpsf, jun, mcm4, myc, p21, ccne2, cdk6, and col1, among others. It was speculated that the absence of maternal Mep50 could potentially lead to errors in DNA replication and cell cycle arrest, ultimately resulting in cell apoptosis. This eventually resulted in the failure of gastrulation and embryonic death. The results indicate the importance of maternal Mep50 in early embryonic development, particularly in medaka fish.

Keywords: DNA replication; Mep50; RNA sequencing; cell cycle; embryonic development.