In vivo T-box transcription factor profiling reveals joint regulation of embryonic neuromesodermal bipotency.
The design of effective cell replacement therapies requires detailed knowledge of how embryonic stem cells form primary tissues, such as mesoderm or neurectoderm that later become skeletal muscle or nervous system. Members of the T-box transcription factor family are key in the formation of these primary tissues, but their underlying molecular activities are poorly understood. Here, we define in vivo genome-wide regulatory inputs of the T-box proteins Brachyury, Eomesodermin, and VegT, which together maintain neuromesodermal stem cells and determine their bipotential fates in frog embryos. These T-box proteins are all recruited to the same genomic recognition sites, from where they activate genes involved in stem cell maintenance and mesoderm formation while repressing neurogenic genes. Consequently, their loss causes embryos to form an oversized neural tube with no mesodermal derivatives. This collaboration between T-box family members thus ensures the continuous formation of correctly proportioned neural and mesodermal tissues in vertebrate embryos during axial elongation.
Division of Systems Biology, National Institute for Medical Research, London NW7 1AA, UK; Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge CB2 1QN, UK; Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK. Electronic address: ggentsc@nimr.mrc.ac.uk.
George E
GE
Gentsch
Nick D L
ND
Owens
Stephen R
SR
Martin
Paul
P
Piccinelli
Tiago
T
Faial
Matthew W B
MW
Trotter
Michael J
MJ
Gilchrist
James C
JC
Smith
D000818:Animals; D004247:DNA / Q000235:genetics / Q000378:metabolism; D047108:Embryonic Development / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D054259:Neural Tube / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus
D020825:T-Box Domain Proteins; D004247:DNA