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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 05, 2017 |
| Title |
Patterning and gastrulation defects caused by the tw18 lethal are due to loss of Ppp2r1a |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The mouse t haplotype, a variant 20 cM genomic region on Chromosome 17, harbors sixteen 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. We have used a candidate gene approach, gene knockout by homologous recombination and genetic rescue to identify the gene causing the tw18 phenotype as Ppp2r1a, encoding the PP2A scaffolding subunit PR65. 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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| Overall design |
The transcriptomes of E6.5 epiblast cells from WT, tw18/+ and tw18/tw18 embryos, obtained via matings, were analyzed by strand-specific RNA-Seq of ribosomal RNA-depleted total RNA.
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| Contributor(s) |
Lange L, Marks M, Liu J, Bauer H, Wittler L, Piehl S, Timmermann B, Herrmann BG |
| Citation(s) |
28619992 |
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| Submission date |
Nov 09, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Jinhua Liu |
| Organization name |
Max Planck Institute for Molecular Genetics
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| Street address |
Ihnestra§e 73
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| City |
Berlin |
| ZIP/Postal code |
14159 |
| Country |
Germany |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA353031 |
| SRA |
SRP093263 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE89734_tw18_gene_FPKM.txt.gz |
298.9 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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