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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 05, 2014 |
| Title |
The transcriptional response to Norrin/Fz4 signaling |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Using mice with targeted gene mutations, we identify (1) distinct roles for different canonical Wnt signaling components in central nervous system (CNS) vascular development and in the specification of the blood-brain and blood-retina barriers (BBB and BRB) and (2) differential sensitivities of the vasculature in various CNS regions to perturbations in canonical Wnt signaling components. We find nearly equivalent roles for Lrp5 and Lrp6 in brain vascular development and barrier maintenance but a dominant role for Lrp5 in the retinal vasculature, an especially high sensitivity of the BBB in the cerebellum and pons/interpeduncular nuclei to decrements in canonical Wnt signaling, and plasticity in the barrier properties of mature CNS vasculature. Brain and retinal vascular defects caused by loss of Norrin/Frizzled4 signaling can be fully rescued by stabilizing beta-catenin, and loss of beta-catenin’s transcriptional activation domain or expression of a dominant negative Tcf4 recapitulates the vascular development and barrier defects seen with loss of receptor, co-receptor, or ligand, indicating that Norrin/Frizzled4 signaling acts predominantly by beta-catenin-dependent transcriptional regulation. This work strongly supports a model in which identical or nearly identical canonical Wnt signaling mechanisms mediate neural tube and retinal vascularization and maintain the BBB and BRB.
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| Overall design |
Total retina RNA from P10 WT, NdpKO, Ctnnb1flex3/+;Pdgfb-CreER, and NdpKO;Ctnnb1flex3/+;Pdgfb-CreER mice was subjected to RNAseq
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| Contributor(s) |
Zhou Y, Nathans J |
| Citation(s) |
25083995 |
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| Submission date |
Apr 02, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Yulian Zhou |
| E-mail(s) |
yzhou.jhmi@gmail.com
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| Phone |
4109554678
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| Organization name |
JHMI
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| Street address |
725 N. Wolfe Street
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| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21205 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA243364 |
| SRA |
SRP040810 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE56461_genes.fpkm_tracking.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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