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Series GSE225367 Query DataSets for GSE225367
Status Public on Apr 19, 2024
Title GPR124 regulates murine CNS angiogenesis and blood-brain barrier formation by an intracellular domain-independent mechanism
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The GPR124/RECK/WNT7 pathway essentially regulates central nervous system angiogenesis and blood-brain barrier (BBB) function. GPR124, a brain endothelial adhesion 7-pass transmembrane protein, associates with membrane RECK, which binds and stabilizes newly synthesized WNT7 for subsequent transfer to Frizzled (FZD) and canonical b-catenin signaling. GPR124 function remains enigmatic; while its extracellular domain (ECD) is required, the poorly conserved intracellular domain (ICD) appears to be variably required in mammals versus zebrafish, potentially mediated by bridging of the GPR124 and FZD ICDs by intracellular adaptor proteins. GPR124 ICD deletion mutants impair zebrafish angiogenesis, but paradoxically still mediate WNT7 signaling upon mammalian cell transfection. We thus further investigated the GPR124 C-terminal ICD by deletion in mice (Gpr124ΔC). Notably, Gpr124ΔC/ΔC mice could be born and did not recapitulate Gpr124-/- embryonic lethal forebrain hemorrhage. GPR124ΔC protein was inefficiently expressed, resulting in mild, hypomorphic, non-hemorrhagic defects in CNS angiogenesis and BBB function, sparing the cortex and only confined to ganglionic eminences. Impaired surface expression of GPR124ΔC directly correlated with reduced endothelial WNT signaling, arguing against an intrinsic signaling deficiency. Further, GPR124ΔC and recombinant GPR124 ECD both rescued WNT7 signaling following brain endothelial Gpr124 knockdown. Thus, in mice, the GPR124 essential regulation of WNT7-dependent CNS forebrain angiogenesis and BBB function is exerted by ICD-independent functionality, extending the range of signaling mechanisms used by adhesion 7-pass transmembrane receptors.
Overall design Comparative gene expression profiling of RNA-seq data for embryonic brain endothelial cells from WT, Gpr124 C-terminal ICD deletion (ΔC/ΔC) and Gpr124 knockout (-/-) mice.
Contributor(s) Yuki K, Tang AT, Kahn ML, Kuo C
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Submission date Feb 15, 2023
Last update date Apr 20, 2024
Contact name Kanako Yuki
Phone 6507704125
Organization name Stanford University
Street address 265 CAMPUS DRIVE
City Stanford
State/province CA
ZIP/Postal code 94305
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (12)
GSM7047570 WT bECs E15.5 JE1
GSM7047571 WT bECs E15.5 JE6
GSM7047572 WT bECs E15.5 KE8
BioProject PRJNA935353

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE225367_RAW.tar 40.0 Mb (http)(custom) TAR (of TXT)
GSE225367_TPM_values.csv.gz 1.2 Mb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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