GSE93524 Antagonistic activities of Sox2 and Brachyury control the fate choice of neuro-mesodermal progenitors

Contributors : Frederic Koch ; Manuela Scholze ; Lars Wittler ; Dennis Schifferl ; Smita Sudheer ; Phillip Grote ; Bernd Timmermann ; Karol Macura ; Bernhard G Herrmann
Series Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencing
Organism : Mus musculus

The spinal cord and mesodermal tissues of the trunk such as the vertebral column and skeletal musculature derive from neuro-mesodermal progenitors (NMPs). Sox2, Brachyury (T) and Tbx6 have been correlated with NMP potency and lineage choice, however, their exact role and interaction in these processes have not been revealed yet. Here we present a global analysis of NMPs and their descending lineages performed on purified cells from E8.5 wild-type and mutant embryos. We show that T, cooperatively with WNT signaling, controls the progenitor state and the switch towards the mesodermal fate. Sox2 acts antagonistically and promotes neural development. Tbx6 reinforces the mesodermal fate choice, represses the progenitor state and confers paraxial fate commitment. Our findings refine previous models and establish new concepts of the molecular principles of mammalian trunk development comprising NMP maintenance, lineage choice and mesoderm formation.

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