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XB-ART-47416
Cell Rep September 26, 2013; 4 (6): 1185-96.

In vivo T-box transcription factor profiling reveals joint regulation of embryonic neuromesodermal bipotency.

Gentsch GE , Owens ND , Martin SR , Piccinelli P , Faial T , Trotter MW , Gilchrist MJ , Smith JC .


Abstract
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.

PubMed ID: 24055059
PMC ID: PMC3791401
Article link: Cell Rep
Grant support: [+]
Genes referenced: actl6a aldh1a2 cav1 copb1 cyp26a1 dlc eomes esr-5 fgf4 fgf8 foxc1 foxh1.2 gdf3 gemin2 h2ac21 h2az1 hes5.8 hes5.9 homer1 hoxd8 hsf2 igf2bp3 klhl20 mespa mespb myf5 myh1 myod1 odc1 pax3 ppm1g ripply2.1 ripply2.2 smad2 smad3 sox3 tal1 tbx6 tbxt tbxt.2 tes tubb2b vegt ventx2.1 ventx2.2 wnt11
Morpholinos: eomes MO1 eomes MO2 tbxt MO2 tbxt MO3 tbxt.2 MO3 tbxt.2 MO4 vegt MO3

GEO Series:
   GSE48560: Xenbase,  NCBI
   GSE48663: Xenbase,  NCBI


Article Images: [+] show captions
References:
Akkers, 2009, Pubmed, Xenbase [+]


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