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Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a
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| Zeitschriftentitel: | Biology Open |
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| Personen und Körperschaften: | , , , , , , , , |
| In: | Biology Open, 6, 2017, 6, S. 752-764 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The Company of Biologists
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| Schlagwörter: |
| author_facet |
Lange, Lisette Marks, Matthias Liu, Jinhua Wittler, Lars Bauer, Hermann Piehl, Sandra Bläß, Gabriele Timmermann, Bernd Herrmann, Bernhard G. Lange, Lisette Marks, Matthias Liu, Jinhua Wittler, Lars Bauer, Hermann Piehl, Sandra Bläß, Gabriele Timmermann, Bernd Herrmann, Bernhard G. |
|---|---|
| author |
Lange, Lisette Marks, Matthias Liu, Jinhua Wittler, Lars Bauer, Hermann Piehl, Sandra Bläß, Gabriele Timmermann, Bernd Herrmann, Bernhard G. |
| spellingShingle |
Lange, Lisette Marks, Matthias Liu, Jinhua Wittler, Lars Bauer, Hermann Piehl, Sandra Bläß, Gabriele Timmermann, Bernd Herrmann, Bernhard G. Biology Open Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a General Agricultural and Biological Sciences General Biochemistry, Genetics and Molecular Biology |
| author_sort |
lange, lisette |
| spelling |
Lange, Lisette Marks, Matthias Liu, Jinhua Wittler, Lars Bauer, Hermann Piehl, Sandra Bläß, Gabriele Timmermann, Bernd Herrmann, Bernhard G. 2046-6390 The Company of Biologists General Agricultural and Biological Sciences General Biochemistry, Genetics and Molecular Biology http://dx.doi.org/10.1242/bio.023200 <jats:title>ABSTRACT</jats:title><jats:p>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.</jats:p> Patterning and gastrulation defects caused by the<i>tw18</i>lethal are due to loss of<i>Ppp2r1a</i> Biology Open |
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| title |
Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a |
| title_unstemmed |
Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a |
| title_full |
Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a |
| title_fullStr |
Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a |
| title_full_unstemmed |
Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a |
| title_short |
Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a |
| title_sort |
patterning and gastrulation defects caused by the<i>tw18</i>lethal are due to loss of<i>ppp2r1a</i> |
| topic |
General Agricultural and Biological Sciences General Biochemistry, Genetics and Molecular Biology |
| url |
http://dx.doi.org/10.1242/bio.023200 |
| publishDate |
2017 |
| physical |
752-764 |
| description |
<jats:title>ABSTRACT</jats:title><jats:p>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.</jats:p> |
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| author | Lange, Lisette, Marks, Matthias, Liu, Jinhua, Wittler, Lars, Bauer, Hermann, Piehl, Sandra, Bläß, Gabriele, Timmermann, Bernd, Herrmann, Bernhard G. |
| author_facet | Lange, Lisette, Marks, Matthias, Liu, Jinhua, Wittler, Lars, Bauer, Hermann, Piehl, Sandra, Bläß, Gabriele, Timmermann, Bernd, Herrmann, Bernhard G., Lange, Lisette, Marks, Matthias, Liu, Jinhua, Wittler, Lars, Bauer, Hermann, Piehl, Sandra, Bläß, Gabriele, Timmermann, Bernd, Herrmann, Bernhard G. |
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| description | <jats:title>ABSTRACT</jats:title><jats:p>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.</jats:p> |
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| spelling | Lange, Lisette Marks, Matthias Liu, Jinhua Wittler, Lars Bauer, Hermann Piehl, Sandra Bläß, Gabriele Timmermann, Bernd Herrmann, Bernhard G. 2046-6390 The Company of Biologists General Agricultural and Biological Sciences General Biochemistry, Genetics and Molecular Biology http://dx.doi.org/10.1242/bio.023200 <jats:title>ABSTRACT</jats:title><jats:p>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.</jats:p> Patterning and gastrulation defects caused by the<i>tw18</i>lethal are due to loss of<i>Ppp2r1a</i> Biology Open |
| spellingShingle | Lange, Lisette, Marks, Matthias, Liu, Jinhua, Wittler, Lars, Bauer, Hermann, Piehl, Sandra, Bläß, Gabriele, Timmermann, Bernd, Herrmann, Bernhard G., Biology Open, Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a, General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology |
| title | Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a |
| title_full | Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a |
| title_fullStr | Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a |
| title_full_unstemmed | Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a |
| title_short | Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a |
| title_sort | patterning and gastrulation defects caused by the<i>tw18</i>lethal are due to loss of<i>ppp2r1a</i> |
| title_unstemmed | Patterning and gastrulation defects caused by thetw18lethal are due to loss ofPpp2r1a |
| topic | General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology |
| url | http://dx.doi.org/10.1242/bio.023200 |