Spx

Spatial tier: STRICT_EXCLUSIVE · Class: OTHER · Top region: MH (Medial habenula) · Positive regions: 8/554

43.5Discovery Score
39.4Targetability Score
CEvidence grade C
What this means: Spx: predicted fine-region profile is strict-exclusive, with 8 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in MH: evidence, prediction, innovation

Gene function
Spx encodes spexin (NPQ/C12orf39), a secreted 14-amino-acid galanin/kisspeptin-superfamily neuropeptide. It agonizes Gi/o-coupled GALR2 and GALR3, not GALR1, lowering cAMP and dampening firing. Spexin is linked to satiety, nociception, anxiety and mood.
Region function
Medial habenula carries septal and limbic input via the fasciculus retroflexus to the interpeduncular nucleus, controlling fear/anxiety, nicotine aversion/withdrawal, mood and exercise motivation.
Published in this region
expression only Yun et al. 2019 mapped SPX mRNA (ISH/qRT-PCR): enriched in medial habenula and suprachiasmatic nucleus; GALR2 high in habenula, hypothalamus, ventral midbrain, dorsal raphe; their GALR2 agonist SG2A was anxiolytic and antidepressant i.c.v., not MHb-targeted. Zebrafish dorsal habenula expresses spx1; Jeong et al. 2019: dHb spexin-1 overexpression reduces anxiety-like behaviour; Kim et al. 2019 mapped the spx1 dHb-interpeduncular circuit.
Predicted function
Prediction: spexin is an MHb co-transmitter (likely cholinergic/substance P cells) acting on GALR2/3 in the interpeduncular nucleus or locally, slow inhibitory feedback setting habenular excitability during stress and aversion. Conditional MHb Spx deletion should raise anxiety and MHb-IPN drive; MHb-targeted spexin or SG2A should be anxiolytic and blunt nicotine withdrawal, as in zebrafish.
Innovation
★★★★☆ 4/5 Mouse MHb spexin rests on one pharmacology paper and has never been manipulated there, while habenular tools are mature.
Tools
No Spx-Cre line; spexin peptide, the GALR2-selective spexin analogue SG2A, GALR2/GALR3 ligands and mouse-validated anti-spexin antibodies. MHb access via Tac1-Cre, Tac2-Cre or Chat-Cre.
References

Direct evidence located at the region

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

Look it up yourself: Allen Mouse Brain ISH for SpxAllen reference atlas: MH (structure 483)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Spx" or by parcellation_substructure "MH")All genes confined to MH + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
MH MERFISH region locator
Real single-cell MERFISH coordinates for the MH (Medial habenula) 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

Spx regional expression profile

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

Spatial profile

MH
1.66
B
1.59
PBG
1.35
Su3
0.915
PF
0.897
PDTg
0.851
SNc
0.783
LC
0.696
LDT
0.694
VTA
0.691
CU
0.69
PSV
0.653
PS
0.644
ICc
0.642
Pa5
0.637
PPN
0.626
DR
0.626
LH
0.623
VPMpc
0.621
MA
0.619

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.328
Top-region fraction
0.087
Filter status
PASS

Interpretation limits