Lpar4

Lysophosphatidic acid receptor 4 (LPA receptor 4) (LPA-4) (G protein-coupled receptor 23) (P2Y purinoceptor 9) (P2Y9) (Purinergic receptor 9)

Spatial tier: REGION_BIASED · Class: GPCR · Top region: ME (Median eminence) · Positive regions: 55/554

44.7Discovery Score
39.7Targetability Score
CEvidence grade C
What this means: Lpar4: fine CCF profile is region-biased toward ME (top regions: ME, ENTl1, IG, SCO, ENTm1); this is a discovery lead, not direct proof.

Function in ME: evidence, prediction, innovation

Gene function
Lpar4 (formerly P2Y9/GPR23) encodes a non-EDG-family lysophosphatidic acid receptor coupling mainly to G12/13-RhoA, and also Gs and Gq. It is the vascular LPA receptor: Lpar4-deficient embryos show haemorrhage, oedema, dilated vessels and impaired pericyte and smooth-muscle coverage, and LPA4 regulates YAP/TAZ- and Notch-dependent angiogenesis. LPAR4 protein is also expressed by developing cortical and hippocampal neurons.
Region function
The median eminence is the neurohaemal interface of the hypothalamus, where fenestrated, highly permeable portal capillaries collect hypophysiotropic hormones and tanycyte endfeet wrap the vasculature to control barrier properties.
Published in this region
expression only No functional study of Lpar4 in the ME. The closest evidence is that LPA4 is selectively expressed by brain vascular endothelium and required for LPA-mediated preservation of blood-brain barrier integrity and claudin-5 after stroke (Yamada 2026), plus Allen ISH showing ME expression energy 0.78-0.96 versus 0.51 for grey matter (experiment 69257510).
Predicted function
Prediction: the median eminence signal is vascular, reflecting LPA4 on fenestrated portal endothelium and its mural cells, where G12/13-RhoA signalling sets junctional tension and mural coverage and therefore how permeable this organ stays. Endothelial Lpar4 deletion should exaggerate leakiness and tanycyte barrier rearrangement, altering the fasting-induced permeability switch, with little direct effect on neuronal firing.
Innovation
★★★★★ 5/5 LPA4 has never been studied in any circumventricular organ despite the median eminence being the brain's most specialised fenestrated vascular bed.
Tools
Lpar4 knockout mice, viable with partial embryonic vascular lethality (Sumida 2010; Yamada 2026); anti-LPAR4 antibodies validated on mouse brain (Ishidou 2025); LPA and autotaxin inhibitors as non-selective pharmacology; no selective LPA4 agonist or antagonist is established.
References

Direct evidence located at the region

Lpar4 Allen ISH at the CCF centroid of ME

Allen ISH experiment 69257510, section image 69240403 (section 117): 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

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

Lpar4 regional expression profile

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

Spatial profile

ME
2.35
ENTl1
1.39
IG
1.25
SCO
1.25
ENTm1
1.22
LM
1.22
SSp-m1
1.21
VISC1
1.2
AUDd1
1.19
VISpor1
1.18
SSs1
1.18
SSp-bfd1
1.17
AUDp1
1.17
VISam1
1.17
AIp1
1.16
VISp1
1.16
GU1
1.15
SSp-ul1
1.14
SSp-tr1
1.14
SSp-n1
1.14

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.284
Top-region fraction
0.042
Filter status
PASS

Interpretation limits