Mrgprd

Mas-related G protein-coupled receptor member D (Beta-alanine receptor) (G protein-coupled receptor TGR7)

Spatial tier: RESTRICTED · Class: GPCR · Top region: LM (Lateral mammillary nucleus) · Positive regions: 21/554

48.6Discovery Score
33.9Targetability Score
CEvidence grade C
What this means: Mrgprd: fine CCF profile is restricted toward LM (top regions: LM, MMd, ME, NLOT1, HATA; 21 positive regions); direct spatial validation is still required.

Function in LM: evidence, prediction, innovation

Gene function
MRGPRD is a Mas-related G-protein-coupled receptor activated by the amino acid beta-alanine, signalling through Gq and Gi. In mouse it is the defining marker of the non-peptidergic, IB4-binding class of C-fibre nociceptors, which innervate the epidermis exclusively and are required for normal mechanical pain sensitivity and for beta-alanine-evoked itch.
Region function
The lateral mammillary nucleus is the mammillary head-direction relay: it receives vestibular information via the dorsal tegmental nucleus and projects through the mammillothalamic tract to the anterodorsal thalamus, generating the earliest directional-heading signal in the Papez circuit.
Published in this region
inferred No region-specific literature found. Mrgprd expression has been validated only in a discrete subset of dorsal root and trigeminal ganglion nociceptors, where Zylka et al. 2005 used targeted axonal tracers to define their epidermal circuits and Cavanaugh et al. 2009 showed they mediate mechanical but not thermal nociception; no central neuronal expression has been confirmed in any species.
Predicted function
Prediction: a genuine MRGPRD signal in the lateral mammillary nucleus would most plausibly indicate a small Gq-coupled population in which beta-alanine or a related metabolite acts as a slow neuromodulator raising excitability in head-direction relay cells, linking metabolic amino-acid status to vestibular signal gain. Local beta-alanine infusion or chemogenetic activation of Mrgprd-CreERT2 cells in LM is predicted to increase firing rate and destabilise head-direction tuning during passive rotation, while Mrgprd-DTR-mediated ablation should have no effect on peripheral touch but may reduce spatial-orientation accuracy; verifying the transcript by RNAscope is the necessary first step, since the prior probability of a true central signal is low.
Innovation
★★★★☆ 4/5 Excellent mouse genetic tools exist and the finding would be genuinely surprising, but MRGPRD is so firmly established as a DRG-restricted gene that the mapped signal may well be noise.
Tools
Mrgprd-EGFPf, Mrgprd-CreERT2 and Mrgprd-DTR mice (Zylka lab); beta-alanine as agonist; MRGPRD antagonists are limited; anti-MRGPRD antibodies are poorly validated; RNAscope with the Mrgprd probe is the appropriate verification assay.
References

Direct evidence located at the region

Mrgprd Allen ISH at the CCF centroid of LM

Allen ISH experiment 76003353, section image 75977062 (section 157): the section that contains the CCF centroid of Lateral mammillary nucleus 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
LM MERFISH region locator
Real single-cell MERFISH coordinates for the LM (Lateral mammillary nucleus) 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

Mrgprd regional expression profile

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

Spatial profile

LM
0.118
MMd
0.0747
ME
0.0656
NLOT1
0.0654
HATA
0.0608
TTv
0.0525
PA
0.0422
COApm
0.0344
SCzo
0.0342
TU
0.0322
CENT3
0.0319
SIM
0.0317
CUL4, 5
0.0315
CENT2
0.0313
ANcr1
0.0306
PFL
0.0296
FL
0.0294
PRM
0.0288
PVp
0.0287
UVU
0.0283

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.310
Top-region fraction
0.068
Filter status
PASS

Interpretation limits