PRD-Class Homeobox Genes in Bovine Early Embryos: Function, Evolution, and Overlapping Roles

Lewin, TD; Fouladi-Nashta, AA; Holland, PWH

Abstract

Eutherian Totipotent Cell Homeobox (ETCHbox) genes are mammalian-specific PRD-class homeobox genes with conserved expression in the preimplantation embryo but fast-evolving and highly divergent sequences. Here, we exploit an ectopic expression approach to examine the role of bovine ETCHbox genes and show that ARGFX and LEUTX homeodomain proteins upregulate genes normally expressed in the blastocyst; the identities of the regulated genes suggest that, in vivo, the ETCHbox genes play a role in coordinating the physical formation of the blastocyst structure. Both genes also downregulate genes expressed earlier during development and genes associated with an undifferentiated cell state, possibly via the JAK/STAT pathway. We find evidence that bovine ARGFX and LEUTX have overlapping functions, in contrast to their antagonistic roles in humans. Finally, we characterize a mutant bovine ARGFX allele which eliminates the homeodomain and show that homozygous mutants are viable. These data support the hypothesis of functional overlap between ETCHbox genes within a species, roles for ETCHbox genes in blastocyst formation and the change of their functions over evolutionary time.

Citation

Lewin, T., Fouladi-Nashta, A., & Holland, P. (2022). PRD-Class Homeobox Genes in Bovine Early Embryos: Function, Evolution, and Overlapping Roles. Molecular Biology and Evolution, 39(5), https://doi.org/10.1093/molbev/msac098

• Journal Article Type: Article
• Acceptance Date: Apr 20, 2022
• Publication Date: May 5, 2022
• Deposit Date: Aug 18, 2022
• Publicly Available Date: Aug 18, 2022
• Print ISSN: 0737-4038
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 39
• Issue: 5
• DOI: https://doi.org/10.1093/molbev/msac098
• Keywords: homeodomain; blastocyst; Crx; genetic redundancy; protein evolution; gene; FALSE DISCOVERY RATE; STEM-CELLS; PREIMPLANTATION DEVELOPMENT; GENOME ACTIVATION; DAIRY-COWS; EXPRESSION; PROTEIN; PANTHER; CATTLE; CYTOSKELETON