Gpr50

Melatonin-related receptor (G protein-coupled receptor 50) (H9)

Spatial tier: STRICT_EXCLUSIVE · Class: GPCR · Top region: OV (Vascular organ of the lamina terminalis) · Positive regions: 5/554

51.8Discovery Score
47.9Targetability Score
CEvidence grade C
What this means: Gpr50: predicted fine-region profile is strict-exclusive, with 5 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in OV: evidence, prediction, innovation

Gene function
GPR50 is an X-linked orphan class A GPCR, ~45% identical to MT1/MT2 but not melatonin-binding. It heterodimerises with MT1 to block MT1 signalling, couples to Galpha12/13-RhoA, and binds TIP60 and the glucocorticoid receptor. In leptin/TRH signalling, Gpr50-null mice are lean, obesity-resistant, hyperactive and fasting-torpor-prone.
Region function
The OVLT is a barrier-free circumventricular organ sensing plasma osmolality, sodium, angiotensin II and relaxin, driving thirst, vasopressin release, thermoregulation and fever.
Published in this region
expression only Batailler et al. 2012, with a validated anti-GPR50 antibody in sheep, rat and mouse, found GPR50 in the OVLT, medial preoptic area, lateral septum, BNST, lateral hypothalamus and amygdala; Sidibe et al. 2010 found strongest adult signal in third-ventricle tanycytes, median eminence and dorsomedial hypothalamus. Function untested here.
Predicted function
Prediction: GPR50 works at the ventricular-vascular interface, where Galpha12/13-RhoA signalling sets barrier permeability and gates blood-borne signals to lamina terminalis neurons. Knockout torpor and thermogenesis phenotypes (Bechtold et al. 2012) suggest it tunes defence thresholds to energy state. Knockdown should shift the osmotic drinking/vasopressin threshold and lower the fasting torpor threshold.
Innovation
★★★★☆ 4/5 GPR50 has a clear metabolic phenotype and OVLT immunoreactivity, yet nobody has manipulated it there.
Tools
Gpr50 knockout/lacZ reporter mouse (Ivanova et al. 2008); validated anti-ovine GPR50 antibody (Batailler et al. 2012); no Cre line, agonist or antagonist; tanycyte access via Rax-CreER or third-ventricle AAV.
References

Direct evidence located at the region

Gpr50 Allen ISH at the CCF centroid of OV

Allen ISH experiment 74511770, section image 74396529 (section 357): 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 74511770, image 74395865 -- target region: OV (Vascular organ of the lamina terminalis)
Allen ISH experiment 74511770, image 74395865 -- target region: OV (Vascular organ of the lamina terminalis)
DIRECT ALLEN ISH
Allen ISH experiment 74511770, image 74396469 -- target region: OV (Vascular organ of the lamina terminalis)
Allen ISH experiment 74511770, image 74396469 -- target region: OV (Vascular organ of the lamina terminalis)

Regional expression figure

Gpr50 regional expression profile

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

Spatial profile

OV
4.09
ME
2.53
PVi
1.35
ARH
1.17
AP
1.15
PVp
0.737
DMH
0.67
SFO
0.619
ADP
0.431
AVPV
0.41
AVP
0.272
MPO
0.23
VLPO
0.201
LPO
0.187
IG
0.174
MEPO
0.174
LDT
0.151
PVpo
0.141
ENTl1
0.138
ENTm1
0.136

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.457
Top-region fraction
0.216
Filter status
PASS

Interpretation limits