Pivotal roles for eomesodermin during axis formation, epithelium-to-mesenchyme transition and endoderm specification in the mouse.
The T-box transcription factor eomesodermin (Eomes) has been implicated as an important component in germ layer induction and patterning in vertebrate embryos. In the mouse, Eomes is essential for development of the trophectoderm lineage and Eomes loss-of-function mutants arrest at implantation. Here, we have used a novel Eomes conditional allele to test Eomes functions in the embryo proper. Eomes-deficient embryos express both Fgf8 and its downstream target Snail at normal levels but surprisingly fail to downregulate E-cadherin. Eomes functional loss thus efficiently and profoundly blocks EMT and concomitant mesoderm delamination. Marker analysis as well as fate-mapping and chimera studies demonstrate for the first time that Eomes is required for specification of the definitive endoderm lineage. We also describe developmental abnormalities in Eomes/Nodal double heterozygotes, and demonstrate that these phenotypes reflect Eomes and Nodal interactions in different tissue sites. Collectively, our experiments establish that Eomes is a key regulator of anteroposterior axis formation, EMT and definitive endoderm specification in the mouse.
Arnold
Sebastian J
SJ
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Hofmann
Ulf K
UK
Bikoff
Elizabeth K
EK
Robertson
Elizabeth J
EJ
D000483:Alleles; D000818:Animals; D019521:Body Patterning; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D015536:Down-Regulation; D020964:Embryo Loss; D004622:Embryo, Mammalian / Q000473:pathology / Q000648:ultrastructure; D004707:Endoderm / Q000196:embryology*; D004848:Epithelium / Q000196:embryology*; D054262:Gastrulation; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005855:Germ Layers / Q000166:cytology; D006579:Heterozygote; D019426:Integrases / Q000378:metabolism; D008648:Mesoderm / Q000196:embryology* / Q000648:ultrastructure; D051379:Mice; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D055457:Nodal Protein; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015820:Cadherins; C491198:Eomes protein, mouse; D055457:Nodal Protein; C526008:Nodal protein, mouse; D020825:T-Box Domain Proteins; D016212:Transforming Growth Factor beta; C045073:Cre recombinase; D019426:Integrases