Antagonistic Activities of Sox2 and Brachyury Control the Fate Choice of Neuro-Mesodermal Progenitors.

Abstract:

: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 yet been revealed. Here we present a global analysis of NMPs and their descending lineages performed on purified cells from embryonic day 8.5 wild-type and mutant embryos. We show that T, cooperatively with WNT signaling, controls the progenitor state and the switch toward the mesodermal fate. Sox2 acts antagonistically and promotes neural development. T is also involved in remodeling the chromatin for mesodermal development. Tbx6 reinforces the mesodermal fate choice, represses the progenitor state, and confers paraxial fate commitment. Our findings refine previous models and establish molecular principles underlying mammalian trunk development, comprising NMP maintenance, lineage choice, and mesoderm formation.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Koch F,Scholze M,Wittler L,Schifferl D,Sudheer S,Grote P,Timmermann B,Macura K,Herrmann BG

doi

10.1016/j.devcel.2017.07.021

subject

Has Abstract

pub_date

2017-09-11 00:00:00

pages

514-526.e7

issue

5

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(17)30597-X

journal_volume

42

pub_type

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