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Status |
Public on Jan 31, 2019 |
Title |
The Wnt/ß-catenin axis modulates early BBB development by fine-tuning TGFß signalling through ADAMTSL2 |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
The Wnt/ß-catenin pathway is orchestrating the development of the blood-brain barrier (BBB), but its downstream mediators have remained elusive. To identify potential effectors, we generated an endothelial cell specific Axin1 over-expressing mouse model, AOEiEC. We found that in AOEiE mice Wnt/ß-catenin signalling was down regulated leading to premature regression and remodelling without directly compromising BBB integrity. Interestingly, by comparing transcriptomes of endothelial cells from control and AOEiEC mice, we identified Adamtsl2 as a novel Wnt/ß-catenin-induced, secreted factor, important for stabilizing the cerebral vasculature during development. Importantly, loss-of-function and gain-of-function experiments revealed that Adamtsl2 alone was sufficient to rescue CNS vascular defects seen upon Wnt-signalling inhibition. Furthermore, using various cell and animal models we demonstrate that Adamtsl2 exerts its function by fine-tuning the TGFβ signalling pathway in CNS vessels. In conclusion, this study implicates Adamtsl2 as a mediator of Wnt/ß-catenin signalling during BBB development by linking it to TGFβ signalling.
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Overall design |
We performed RNA-seq for wildtype E14.5 mouse embryos and ones overexpressing Axin1
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Contributor(s) |
Hupe M, Stenman J, Xueting-Li M, Kele-Olovsson J, Hot B |
Citation missing |
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Submission date |
Feb 12, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Julianna MV Kele-Olovsson |
E-mail(s) |
julianna.kele@ki.se
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Organization name |
LICR ltd and Karolinska Institutet
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Department |
Physiology and Pharmacology
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Street address |
Nanna Svartz väg 2
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City |
Stockholm |
ZIP/Postal code |
177 71 |
Country |
Sweden |
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Platforms (1) |
GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
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Samples (6)
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Relations |
BioProject |
PRJNA311937 |
SRA |
SRP070058 |