Adm

Spatial tier: REGION_BIASED · Class: OTHER · Top region: ME (Median eminence) · Positive regions: 34/554

45.3Discovery Score
39.2Targetability Score
CEvidence grade C
What this means: Adm: fine CCF profile is region-biased toward ME (top regions: ME, LM, PO, VPM, VAL); this is a discovery lead, not direct proof.

Function in ME: evidence, prediction, innovation

Gene function
Adm encodes preproadrenomedullin, processed into adrenomedullin and PAMP. Adrenomedullin is a calcitonin/CGRP-family peptide signalling through calcitonin receptor-like receptor with RAMP2 or RAMP3 to raise cAMP; it is a potent vasodilator and stabiliser of endothelial junctions. Global deletion is embryonically lethal; endothelial deletion gives leaky vessels.
Region function
The median eminence is a circumventricular organ where hypophysiotropic axons release GnRH, TRH, CRH, somatostatin and dopamine into fenestrated portal capillaries, and where tanycytes gate access of blood-borne signals to the mediobasal hypothalamus.
Published in this region
direct Ueta 2000 found abundant adrenomedullin-immunoreactive fibres and varicosities in the hypothalamo-neurohypophysial tract and specifically the internal zone of the median eminence, and showed ICV adrenomedullin activates PVN/SON oxytocin cells. Shan 2001 mapped high preproADM mRNA in PVN and SON, the neurons projecting through the median eminence, downregulated by LPS, restraint and dehydration. Allen ISH gives ME 1.77-2.00 versus 0.28 for grey matter (experiment 68667655).
Predicted function
Prediction: median eminence adrenomedullin derives both from passing neurosecretory axons and from portal endothelium, acting through CALCRL-RAMP2 to set capillary tone and permeability and thus hormone entry into portal blood. Endothelial or neuronal Adm deletion, or local AM(22-52), should change barrier leakiness and blunt stress- and osmotically driven output, appearing as exaggerated drinking and altered vasopressin/oxytocin release.
Innovation
★★★☆☆ 3/5 The peptide was localised to the median eminence two decades ago, yet no cell-type-specific loss of function has been done there.
Tools
Adm-null mice (Caron 2001); Adm floxed crossed to endothelial Cre (Ochoa-Callejero 2016); antagonist AM(22-52); adrenomedullin peptide for ICV studies (Samson 1997); Calcrl and Ramp2 mutants; tanycyte access via Rax-CreER lines.
References

Direct evidence located at the region

Adm Allen ISH at the CCF centroid of ME

Allen ISH experiment 74819251, section image 74721590 (section 266): the section that contains the CCF centroid of Median eminence 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 AdmAllen reference atlas: ME (structure 10671)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Adm" or by parcellation_substructure "ME")All genes confined to ME + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
ME MERFISH region locator
Real single-cell MERFISH coordinates for the ME (Median eminence) 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

Adm regional expression profile

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

Spatial profile

ME
1.61
LM
1.31
PO
1.29
VPM
1.15
VAL
1.09
VPL
0.992
PCN
0.962
NLOT1
0.956
MMd
0.947
MGv
0.924
LGd-ip
0.912
MGm
0.887
VPLpc
0.858
SMT
0.839
LGd-co
0.794
MGd
0.783
Eth
0.746
LGd-sh
0.735
RT
0.686
VM
0.682

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.302
Top-region fraction
0.048
Filter status
PASS

Interpretation limits