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  Pattering and gastrulation deffects caused by the tw18 lethal are due to loss of Ppp2r1a

Lange, L., Marks, M., Liu, J., Wittler, L., Bauer, H., Piehl, S., et al. (2017). Pattering and gastrulation deffects caused by the tw18 lethal are due to loss of Ppp2r1a. Biology Open, 6(6), 752-764. doi:10.1242/bio.023200.

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© 2017. Published by The Company of Biologists Ltd

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 Creators:
Lange, Lisette1, 2, Author           
Marks, Matthias1, Author           
Liu, Jinhua1, Author           
Wittler, Lars1, Author           
Bauer, Hermann1, Author           
Piehl, Sandra1, Author           
Bläß, Gabriele1, Author           
Timmermann, Bernd3, Author           
Herrmann, Bernhard G.1, 4, Author           
Affiliations:
1Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              
2Free University Berlin, Department of Biology, Chemistry and Pharmacy, Takustrasse 3, Berlin 14195, Germany, ou_persistent22              
3Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              
4Charité-University Medicine Berlin, Institute for Medical Genetics, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin 12203, Germany, ou_persistent22              

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Free keywords: t haplotype, tw18, Mesoderm, Primitive streak, Signal transduction, PP2A phosphatase
 Abstract: The mouse t haplotype, a variant 20 cM genomic region on Chromosome 17, harbors 16 embryonic control genes identified by recessive lethal mutations isolated from wild mouse populations. Due to technical constraints so far only one of these, the tw5 lethal, has been cloned and molecularly characterized. Here we report the molecular isolation of the tw18 lethal. Embryos carrying the tw18 lethal die from major gastrulation defects commencing with primitive streak formation at E6.5. We have used transcriptome and marker gene analyses to describe the molecular etiology of the tw18 phenotype. We show that both WNT and Nodal signal transduction are impaired in the mutant epiblast, causing embryonic patterning defects and failure of primitive streak and mesoderm formation. By using a candidate gene approach, gene knockout by homologous recombination and genetic rescue, we have identified the gene causing the tw18 phenotype as Ppp2r1a, encoding the PP2A scaffolding subunit PR65alpha. Our work highlights the importance of phosphatase 2A in embryonic patterning, primitive streak formation, gastrulation, and mesoderm formation downstream of WNT and Nodal signaling.

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Language(s): eng - English
 Dates: 2017-04-062017-06-15
 Publication Status: Published online
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1242/bio.023200
PMC: PMC5483016
 Degree: -

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Title: Biology Open
Source Genre: Journal
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Publ. Info: The Company of Biologists
Pages: - Volume / Issue: 6 (6) Sequence Number: - Start / End Page: 752 - 764 Identifier: ISSN: 2046-6390