A 37 kb region upstream of brachyury comprising a notochord enhancer is 
essential for notochord and tail development

Schifferl, Dennis; Scholze-Wittler, Manuela; Wittler, Lars; Veenvliet, Jesse V.; Koch, Frederic; Herrmann, Bernhard G.

doi:10.1242/dev.200059

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A 37 kb region upstream of brachyury comprising a notochord enhancer is essential for notochord and tail development

MPS-Authors

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Schifferl, Dennis
Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Scholze-Wittler, Manuela
Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Wittler, Lars
Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Veenvliet, Jesse V.
Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Koch, Frederic
Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Herrmann, Bernhard G.
Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Schifferl et al_2021.pdf
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引用

Schifferl, D., Scholze-Wittler, M., Wittler, L., Veenvliet, J. V., Koch, F., & Herrmann, B. G. (2021). A 37 kb region upstream of brachyury comprising a notochord enhancer is essential for notochord and tail development. Development, 148(23):. doi:10.1242/dev.200059.

引用: https://hdl.handle.net/21.11116/0000-0009-B873-6

要旨

The node-streak border region comprising notochord progenitor cells (NPCs) at the posterior node and neuro-mesodermal progenitor cells (NMPs) in the adjacent epiblast is the prime organizing center for axial elongation in mouse embryos. The T-box transcription factor brachyury (T) is essential for both formation of the notochord and maintenance of NMPs, and thus is a key regulator of trunk and tail development. The T promoter controlling T expression in NMPs and nascent mesoderm has been characterized in detail; however, control elements for T expression in the notochord have not been identified yet. We have generated a series of deletion alleles by CRISPR/Cas9 genome editing in mESCs, and analyzed their effects in mutant mouse embryos. We identified a 37 kb region upstream of T that is essential for notochord function and tailbud outgrowth. Within that region, we discovered a T-binding enhancer required for notochord cell specification and differentiation. Our data reveal a complex regulatory landscape controlling cell type-specific expression and function of T in NMP/nascent mesoderm and node/notochord, allowing proper trunk and tail development.