Adgre1

Adhesion G protein-coupled receptor E1 (Cell surface glycoprotein F4/80) (EGF-like module receptor 1) (EGF-like module-containing mucin-like hormone receptor-like 1) (EMR1 hormone receptor)

Spatial tier: RESTRICTED · Class: GPCR · Top region: LC (Locus ceruleus) · Positive regions: 13/554

47.3Discovery Score
38.1Targetability Score
CEvidence grade C
What this means: Adgre1: fine CCF profile is restricted toward LC (top regions: LC, SLC, DMX, AId1, TEa1; 13 positive regions); direct spatial validation is still required.

Function in LC: evidence, prediction, innovation

Gene function
ADGRE1 encodes EMR1, better known in mouse as F4/80. It is an adhesion-class G-protein-coupled receptor with a string of extracellular EGF-like repeats and a GAIN domain. F4/80 is the classic pan-macrophage and microglia surface marker in mouse and is required for the induction of peripheral immune tolerance, while the human orthologue EMR1 is restricted to eosinophils; no ligand or downstream signalling output is firmly established for either.
Region function
The locus coeruleus is the principal noradrenergic nucleus of the brain; its small population of neurons innervates nearly the whole forebrain and sets arousal, attention, stress reactivity, sleep-wake transitions and network gain.
Published in this region
inferred No region-specific literature found. Adgre1/F4/80 in brain labels microglia and perivascular and meningeal macrophages rather than neurons (Hamann et al. 2007), and Wasinski et al. 2023 used hypothalamic Adgre1 as a neuroinflammatory marker; a locus coeruleus signal therefore most plausibly reflects the nucleus's dense perivascular macrophage and microglial population rather than noradrenergic neurons themselves.
Predicted function
Prediction: ADGRE1-positive macrophages and microglia in the locus coeruleus are predicted to act as local immune sentinels whose activation state gates noradrenergic excitability, providing a route by which systemic inflammation produces sickness-associated changes in arousal and attention. Microglia-restricted Adgre1 deletion or macrophage depletion with clodronate or CSF1R inhibitors in LC is predicted to leave baseline sleep-wake architecture intact but to blunt the LPS-induced rise in LC firing and the accompanying sickness-related hypersomnolence and reduced exploratory behaviour; F4/80 immunolabelling combined with Dbh-Cre photometry is the natural first experiment.
Innovation
★★★☆☆ 3/5 Neuroimmune modulation of the locus coeruleus is an interesting and under-explored idea, but because Adgre1 almost certainly marks glia rather than LC neurons the finding is less surprising and the reagents are standard immunology tools.
Tools
F4/80 (Adgre1)-Cre and Adgre1-knockout mice; anti-F4/80 antibody clones BM8 and CI:A3-1; Cx3cr1-CreER and Lyve1-Cre for microglia versus perivascular macrophages; clodronate liposomes and CSF1R inhibitors PLX5622/PLX3397 for depletion; Dbh-Cre and Net-Cre plus GRAB-NE for the noradrenergic readout.
References

Direct evidence located at the region

No Allen ISH section could be located at this region's centroid for the recorded experiments.

Direct spatial evidence

MERFISH REGION LOCATOR
LC MERFISH region locator
Real single-cell MERFISH coordinates for the LC (Locus ceruleus) 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

Adgre1 regional expression profile

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

Spatial profile

LC
0.852
SLC
0.833
DMX
0.74
AId1
0.358
TEa1
0.343
AUDv1
0.291
CA1slm
0.289
AUDpo1
0.288
VISli1
0.281
GU1
0.279
VISC1
0.27
ECT1
0.267
MOs1
0.262
VISam1
0.258
SSs1
0.255
VISl1
0.251
MOp1
0.245
SSp-ul1
0.244
AUDd1
0.233
ACAd1
0.229

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.323
Top-region fraction
0.077
Filter status
PASS

Interpretation limits