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Series GSE77874 Query DataSets for GSE77874
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
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.
 
Overall design We performed RNA-seq for wildtype E14.5 mouse embryos and ones overexpressing Axin1
 
Contributor(s) Hupe M, Stenman J, Xueting-Li M, Kele-Olovsson J, Hot B
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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
Organization name LICR ltd and Karolinska Institutet
Department Physiology and Pharmacology
Street address Nanna Svartz väg 2
City Stockholm
ZIP/Postal code 177 71
Country Sweden
 
Platforms (1)
GPL9250 Illumina Genome Analyzer II (Mus musculus)
Samples (6)
GSM2060867 E145_EC-Brain1
GSM2060868 E145_EC-Brain2
GSM2060869 E145_EC-Brain3
Relations
BioProject PRJNA311937
SRA SRP070058

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE77874_wt14_5aoe14_5.txt.gz 1.5 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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