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

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...

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Bibliographic Details
Published inMolecular biology and evolution Vol. 39; no. 5
Main Authors Lewin, Thomas D., Fouladi-Nashta, Ali A., Holland, Peter W.H.
Format Journal Article
LanguageEnglish
Published United States Oxford University Press 03.05.2022
Subjects
Animals
Beef cattle
Blastocyst - metabolism
Cattle
Discoveries
Embryonic development
Embryonic Development - genetics
Gene Expression Regulation, Developmental
Genes, Homeobox
Humans
Janus Kinases - genetics
Janus Kinases - metabolism
Mammals - genetics
Proteins
Signal Transduction
STAT Transcription Factors - genetics
STAT Transcription Factors - metabolism
United Kingdom
Crx
blastocyst
protein evolution
genetic redundancy
gene
homeodomain
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Summary: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.
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ISSN:0737-4038
1537-1719
DOI:10.1093/molbev/msac098