Cx3cr1

CX3C chemokine receptor 1 (C-X3-C CKR-1) (CX3CR1) (mCX3CR1) (Fractalkine receptor)

Spatial tier: RESTRICTED · Class: GPCR · Top region: SCO (Subcommissural organ) · Positive regions: 19/554

41.5Discovery Score

37.7Targetability Score

CEvidence grade C

What this means: Cx3cr1: fine CCF profile is restricted toward SCO (top regions: SCO, AId1, TEa1, CA1slm, AUDpo1; 19 positive regions); direct spatial validation is still required.

Function in SCO: evidence, prediction, innovation

Gene function

Cx3cr1 encodes the Gi-coupled receptor for fractalkine (CX3CL1), a chemokine that is membrane-tethered on neurons and shed as a soluble form. In the CNS it is expressed almost exclusively by microglia and by perivascular and border-associated macrophages, and it mediates neuron-to-microglia signalling that controls microglial surveillance, developmental synaptic pruning and restraint of inflammatory activation.

Region function

The subcommissural organ is a tiny ependymal secretory gland at the entrance of the cerebral aqueduct beneath the posterior commissure; it releases SCO-spondin into the CSF, where it condenses into Reissner's fibre, and its failure causes aqueductal stenosis and hydrocephalus.

Published in this region

expression only No region-specific literature found for the subcommissural organ specifically. The closest finding is Kawai 2020, who documented a transient increase in microglial C1q expression in the circumventricular organs of adult mice during LPS-induced inflammation, showing that CVO-associated microglia are a distinct, inflammation-responsive population; Chakravarty 2005 showed that non-haematopoietic cells at these barrier interfaces sustain CNS inflammation during endotoxaemia. Cx3cr1-GFP mice are the standard means of visualising these cells, so brain-wide reporter expression includes the SCO region.

Predicted function

Prediction: a Cx3cr1 signal at the SCO almost certainly reports resident microglia and border macrophages clustered around this leaky, densely vascularised circumventricular gland rather than the ependymocytes themselves. Functionally, CX3CL1-CX3CR1 signalling there should restrain microglial activation next to a fenestrated-vessel interface. Cx3cr1 deletion or CreER-mediated ablation is predicted to increase local microglial reactivity and cytokine release after systemic LPS, and, because SCO-spondin secretion is sensitive to inflammation, to perturb Reissner's-fibre formation and CSF flow rather than to change behaviour directly.

Innovation

★★★☆☆ 3/5 Microglial CX3CR1 is heavily studied brain-wide, but nobody has asked what the microglia surrounding the subcommissural organ do to CSF secretion.

Tools

Cx3cr1-GFP (JAX 005582), Cx3cr1-CreER (JAX 021160 and JAX 020940) and Cx3cr1 knockout mice; recombinant CX3CL1; anti-CX3CR1 and anti-IBA1 antibodies; microglia-specific AAV enhancer vectors are now available; FoxJ1-CreER (JAX 027012) for the complementary ependymal compartment.

References

Direct evidence located at the region

Cx3cr1 Allen ISH at the CCF centroid of SCO

Allen ISH experiment 1605, section image 101361669 (section 198): the section that contains the CCF centroid of Subcommissural organ 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

Look it up yourself: Allen Mouse Brain ISH for Cx3cr1 Allen reference atlas: SCO (structure 599626923)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Cx3cr1" or by parcellation_substructure "SCO")All genes confined to SCO + 3-D brain

Direct spatial evidence

SCO MERFISH region locator — Real single-cell MERFISH coordinates for the SCO (Subcommissural organ) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.

Regional expression figure

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

Spatial profile

SCO

2.15

AId1

1.45

TEa1

1.4

CA1slm

1.32

AUDpo1

1.3

PVpo

1.28

VISC1

1.28

AUDv1

1.28

GU1

1.28

PERI5

1.27

VISli1

1.27

VISam1

1.26

ILA1

1.25

ECT1

1.25

CA1sr

1.24

SSs1

1.24

MOs1

1.22

VISl1

1.22

BLAv

1.21

SSp-ul1

1.2

Evidence and specificity

Evidence status: PREDICTED_FINE
Direct sources: None; predicted localization only
Exclusive threshold: 12 positive regions out of 554
Spatial specificity: 0.270
Top-region fraction: 0.063
Filter status: PASS

Interpretation limits

Cell-type-to-region projection is imputed expression, not direct spatial measurement.
Adult reference atlases do not establish stability across age, sex, strain, state, or disease.
Transcript abundance does not guarantee protein abundance or genetic-tool performance.