Pomc

Spatial tier: REGION_BIASED · Class: OTHER · Top region: ARH (Arcuate hypothalamic nucleus) · Positive regions: 30/554

42.4Discovery Score
39.1Targetability Score
CEvidence grade C
What this means: Pomc: fine CCF profile is region-biased toward ARH (top regions: ARH, PVH, PD, LC, MH); this is a discovery lead, not direct proof.

Function in ARH: evidence, prediction, innovation

Gene function
Pomc encodes pro-opiomelanocortin, a prohormone cleaved by prohormone convertases into alpha-MSH, ACTH and beta-endorphin. Alpha-MSH is the endogenous agonist at the Gs-coupled melanocortin receptors MC3R/MC4R, while beta-endorphin acts at mu-opioid receptors. Loss of POMC signalling causes hyperphagia and severe early-onset obesity in mice and humans.
Region function
The arcuate nucleus sits at the base of the hypothalamus next to the median eminence, where AgRP/NPY and POMC neurons sense leptin, ghrelin and nutrients to set food intake and energy expenditure; its kisspeptin and dopaminergic neurons also gate GnRH pulses and prolactin.
Published in this region
direct Direct and extensive. Balthasar et al. 2004 showed that deleting the leptin receptor only in POMC neurons causes obesity; Zhan et al. 2013 showed arcuate POMC neurons suppress feeding on a slow timescale while NTS POMC neurons act acutely; Campbell et al. 2017 resolved arcuate POMC cells into several transcriptomic subtypes by Drop-seq.
Predicted function
Prediction (already largely confirmed): Pomc in ARH is the anorexigenic arm of the melanocortin system. Chemogenetic activation of these neurons lowers food intake over hours; arcuate-restricted Pomc deletion gives hyperphagic obesity rescuable by MC4R agonists such as setmelanotide. What remains open is which Lepr+, Glp1r+ or Htr2c+ subpopulation carries each phenotype.
Innovation
★☆☆☆☆ 1/5 POMC in the arcuate nucleus is one of the best-characterised gene-region pairs in metabolic neuroscience.
Tools
Pomc-Cre (JAX 005965, Tg(Pomc1-cre)16Lowl/J), Pomc-eGFP reporters, floxed Pomc and Lepr alleles, intersectional Cre/Dre lines; MC3R/MC4R ligands MTII, SHU9119 and setmelanotide; alpha-MSH and beta-endorphin antibodies.
References

Direct evidence located at the region

Pomc Allen ISH at the CCF centroid of ARH

Allen ISH experiment 2493, section image 101357697 (section 243): the section that contains the CCF centroid of Arcuate hypothalamic 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
ARH MERFISH region locator
Real single-cell MERFISH coordinates for the ARH (Arcuate hypothalamic 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

Pomc regional expression profile

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

Spatial profile

ARH
1.98
PVH
1.44
PD
1.37
LC
1.29
MH
1.29
PVpo
1.28
MEPO
1.23
PMv
1.16
VMPO
1.16
DMH
1.13
DR
1.13
SO
1.12
AVPV
1.11
PVa
1.09
PVi
1.08
MPN
1.08
B
1.04
ME
1.04
VTA
1.02
PVT
0.985

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.301
Top-region fraction
0.055
Filter status
PASS

Interpretation limits