Rln3

Spatial tier: STRICT_EXCLUSIVE · Class: OTHER · Top region: NI (Nucleus incertus) · Positive regions: 2/554

54.6Discovery Score
44.7Targetability Score
CEvidence grade C
What this means: Rln3: predicted fine-region profile is strict-exclusive, with 2 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in NI: evidence, prediction, innovation

Gene function
Rln3 encodes relaxin-3, an insulin-superfamily two-chain peptide and ligand of Gi/o-coupled RXFP3 (also RXFP1/4, lower affinity). RXFP3 lowers cAMP and engages ERK, so relaxin-3 is a slow inhibitory modulator from long-range GABAergic projection neurons.
Region function
The nucleus incertus is a CRF1-rich pontine nucleus projecting to septum, hippocampus, hypothalamus and limbic cortex, pacing hippocampal theta and controlling arousal, locomotor speed, stress and contextual memory.
Published in this region
direct NI holds the brain's largest relaxin-3 population (Smith et al. 2010 mapped Rln3/RXFP3 across arousal, stress and cognitive circuits). Nasirova et al. 2020's Rln3-Cre line shows NI Rln3 neurons are GABAergic, overlap neuromedin-B cells and form the ascending septo-hippocampal system. Callander et al. 2012 silenced NI Rln3 by viral shRNA; Ma et al. 2017, cortical desynchronisation and arousal; Lu et al. 2020, locomotor speed, arousal, hippocampal theta; Szonyi et al. 2019, contextual memory.
Predicted function
Prediction: relaxin-3 from NI terminals inhibits septal and hippocampal targets via RXFP3 to set theta power and arousal gain during stress. Rln3 knockdown or septal RXFP3 antagonism should flatten theta and impair spatial memory, while an RXFP3 agonist should raise theta and food intake.
Innovation
★☆☆☆☆ 1/5 Relaxin-3 defines the nucleus incertus and has been manipulated repeatedly with viral, pharmacological and Cre-based tools.
Tools
Rln3-Cre mice, Rln3 and Rxfp3 knockouts, RXFP3-selective agonists (R3/I5 chimera, RXFP3-A2), antagonist R3(B1-22)R, AAV-shRNA Rln3 constructs, anti-relaxin-3 antibodies.
References

Direct evidence located at the region

Rln3 Allen ISH at the CCF centroid of NI

Allen ISH experiment 73929581, section image 73857864 (section 114): the section that contains the CCF centroid of Nucleus incertus 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

Look it up yourself: Allen Mouse Brain ISH for Rln3Allen reference atlas: NI (structure 604)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Rln3" or by parcellation_substructure "NI")All genes confined to NI + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
NI MERFISH region locator
Real single-cell MERFISH coordinates for the NI (Nucleus incertus) 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

Rln3 regional expression profile

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

Spatial profile

NI
0.369
EW
0.113
LC
0.0618
RO
0.0589
DMX
0.0542
RPO
0.0448
PCG
0.0358
MA
0.0345
PDTg
0.0326
AD
0.0285
SLD
0.0244
SG
0.0243
SCO
0.0237
SLC
0.0203
RPA
0.0188
B
0.0178
NDB
0.0161
PS
0.0153
MRN
0.0139
PVHd
0.0114

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.467
Top-region fraction
0.286
Filter status
PASS

Interpretation limits