Evolution of the mammalian embryonic pluripotency gene regulatory network.
Embryonic pluripotency in the mouse is established and maintained by a gene-regulatory network under the control of a core set of transcription factors that include octamer-binding protein 4 (Oct4; official name POU domain, class 5, transcription factor 1, Pou5f1), sex-determining region Y (SRY)-box containing gene 2 (Sox2), and homeobox protein Nanog. Although this network is largely conserved in eutherian mammals, very little information is available regarding its evolutionary conservation in other vertebrates. We have compared the embryonic pluripotency networks in mouse and chick by means of expression analysis in the pregastrulation chicken embryo, genomic comparisons, and functional assays of pluripotency-related regulatory elements in ES cells and blastocysts. We find that multiple components of the network are either novel to mammals or have acquired novel expression domains in early developmental stages of the mouse. We also find that the downstream action of the mouse core pluripotency factors is mediated largely by genomic sequence elements nonconserved with chick. In the case of Sox2 and Fgf4, we find that elements driving expression in embryonic pluripotent cells have evolved by a small number of nucleotide changes that create novel binding sites for core factors. Our results show that the network in charge of embryonic pluripotency is an evolutionary novelty of mammals that is related to the comparatively extended period during which mammalian embryonic cells need to be maintained in an undetermined state before engaging in early differentiation events.
Department of Cardiovascular Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain.
Beatriz
B
Fernandez-Tresguerres
Susana
S
Cañon
Teresa
T
Rayon
Barbara
B
Pernaute
Miguel
M
Crespo
Carlos
C
Torroja
Miguel
M
Manzanares
D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D017124:Conserved Sequence / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D019143:Evolution, Molecular; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D054262:Gastrulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D016678:Genome / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008322:Mammals / Q000196:embryology* / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity
D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D016222:Fibroblast Growth Factor 2