Cxcr4

C-X-C chemokine receptor type 4 (Fusin) (Leukocyte-derived seven transmembrane domain receptor) (Stromal cell-derived factor 1 receptor)

Spatial tier: STRICT_EXCLUSIVE · Class: GPCR · Top region: OV (Vascular organ of the lamina terminalis) · Positive regions: 9/554

50.2Discovery Score
42.9Targetability Score
CEvidence grade C
What this means: Cxcr4: predicted fine-region profile is strict-exclusive, with 9 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in OV: evidence, prediction, innovation

Gene function
Cxcr4 encodes the Gi-coupled chemokine receptor CXCR4, ligand CXCL12/SDF-1. Activation lowers cAMP, opens GIRK channels, inhibits calcium channels and signals via PI3K/ERK. It guides neuronal migration in development, modulates adult transmitter release, and is the HIV co-receptor.
Region function
The vascular organ of the lamina terminalis is a barrier-free circumventricular organ that, with subfornical organ and median preoptic nucleus, senses osmolality, sodium and angiotensin II to control thirst, vasopressin and sympathetic outflow.
Published in this region
expression only Callewaere et al. 2006 found strong CXCR4 immunoreactivity in the lamina terminalis, including OVLT and subfornical organ (data not shown), proposing these barrier-free sites mediate SDF-1's blunting of angiotensin II-induced vasopressin release; CXCR4 colocalised with >85% of SON and PVN vasopressin neurons, whose firing SDF-1 altered. Banisadr et al. 2002 mapped constitutive neuronal CXCR4 in rat brain; Wei et al. 2012, central SDF-1 drives sympathetic and neurohumoral excitation in heart-failure rats.
Predicted function
Prediction: CXCR4 on OVLT neurons is a blood-facing brake by which circulating CXCL12 tunes osmo- and angiotensin-sensing. Local AMD3100 or OVLT-restricted Cxcr4 deletion should enhance angiotensin-driven drinking and pressor responses; intra-OVLT CXCL12 should suppress firing and water intake.
Innovation
★★★★☆ 4/5 OVLT expression was noted only as unshown data twenty years ago and never tested functionally.
Tools
Cxcr4-floxed mice and Cxcr4-EGFP reporters, antagonist AMD3100 (plerixafor), recombinant CXCL12/SDF-1, anti-CXCR4 antibodies; OVLT is targetable stereotaxically and with circumventricular AAV.
References

Direct evidence located at the region

Cxcr4 Allen ISH at the CCF centroid of OV

Allen ISH experiment 100144881, section image 102234170 (section 130): the section that contains the CCF centroid of Vascular organ of the lamina terminalis according to the Allen image-to-atlas alignment (reference_to_image), with a 2 mm window around that point. Left: whole section, red box = window. Middle: ISH signal. Right: Allen's expression-mask view of the same window. open this image in the Allen viewer

Direct spatial evidence

MERFISH REGION LOCATOR
OV MERFISH region locator
Real single-cell MERFISH coordinates for the OV (Vascular organ of the lamina terminalis) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.
DIRECT ALLEN ISH
Allen ISH experiment 100144881, image 102234170 -- target region: OV (Vascular organ of the lamina terminalis)
Allen ISH experiment 100144881, image 102234170 -- target region: OV (Vascular organ of the lamina terminalis)
DIRECT ALLEN ISH
Allen ISH experiment 100144881, image 102234171 -- target region: OV (Vascular organ of the lamina terminalis)
Allen ISH experiment 100144881, image 102234171 -- target region: OV (Vascular organ of the lamina terminalis)

Regional expression figure

Cxcr4 regional expression profile

Predicted WMB × fine-CCF profile; not direct full-transcriptome spatial measurement.

Spatial profile

OV
2.07
AOBgl
1.58
SCO
1.03
AOBmi
0.993
ME
0.803
PVpo
0.79
AP
0.655
PVi
0.647
SFO
0.64
PVa
0.383
LSc
0.325
PVT
0.289
AD
0.288
LING
0.263
ARH
0.26
GU6b
0.255
RO
0.232
RPA
0.226
AVPV
0.22
PVH
0.218

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.393
Top-region fraction
0.128
Filter status
PASS

Interpretation limits