Fzd5

Frizzled-5 (Fz-5) (mFz5)

Spatial tier: STRICT_EXCLUSIVE · Class: GPCR · Top region: PF (Parafascicular nucleus) · Positive regions: 8/554

48.2Discovery Score
44.2Targetability Score
CEvidence grade C
What this means: Fzd5: predicted fine-region profile is strict-exclusive, with 8 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in PF: evidence, prediction, innovation

Gene function
FZD5 is a seven-pass Wnt receptor that with LRP5/6 transduces canonical Wnt/beta-catenin signalling and can engage Dishevelled-dependent planar-cell-polarity pathways; ligands include Wnt5a, Wnt7 and Wnt9b. It is essential for yolk sac and retinal vascular development and supports neuronal polarity and dendritic morphogenesis.
Region function
The parafascicular nucleus, the caudal intralaminar thalamic nucleus projecting heavily to striatum and cortex, signals salient events and supports attention, sensorimotor coordination, habit formation and flexibility.
Published in this region
direct Liu et al. 2008: Fz5 is expressed in the PFN; conditional deletion causes progressive, cell-autonomous loss of adult PFN neurons, sparing proliferation, migration and axon growth/targeting. Wnt9b, the likely ligand, and beta-catenin transcripts fall in Fz5-null PFN, implying a feedback loop maintaining Wnt components; the motor phenotype showed a PFN sensorimotor role.
Predicted function
Prediction: FZD5 sustains an autocrine Wnt9b-beta-catenin loop keeping adult PF neurons alive, not instructing development. Acute AAV-Cre deletion of floxed Fzd5 in adult PF should cause delayed, progressive degeneration with deficits in attentional set-shifting and habit learning, not gross motor failure. FZD5-selective Wnt surrogates may be neuroprotective in the Parkinson-vulnerable intralaminar thalamus.
Innovation
★★☆☆☆ 2/5 A dedicated conditional-knockout paper establishes the link, leaving only behavioural and degeneration-onset questions.
Tools
Floxed Fzd5 allele with Cre drivers (Liu and Nathans); anti-FZD5 antibodies and recombinant mouse FZD5-Fc are commercial; recombinant Wnt9b/Wnt5a and FZD5 Wnt surrogates; PF access via Slc17a6-Cre or AAV-Cre.
References

Direct evidence located at the region

Fzd5 Allen ISH at the CCF centroid of PF

Allen ISH experiment 1500, section image 101330114 (section 226): the section that contains the CCF centroid of Parafascicular 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
PF MERFISH region locator
Real single-cell MERFISH coordinates for the PF (Parafascicular 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.
DIRECT ALLEN ISH
Allen ISH experiment 1500, image 101330141 -- target region: PF (Parafascicular nucleus)
Allen ISH experiment 1500, image 101330141 -- target region: PF (Parafascicular nucleus)
DIRECT ALLEN ISH
Allen ISH experiment 1500, image 101330147 -- target region: PF (Parafascicular nucleus)
Allen ISH experiment 1500, image 101330147 -- target region: PF (Parafascicular nucleus)

Regional expression figure

Fzd5 regional expression profile

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

Spatial profile

PF
3.86
ME
3.73
ARH
2.52
OV
2.31
VPMpc
1.58
DMH
1.56
PVi
1.07
PCN
1.06
CL
0.955
PVp
0.892
SPFp
0.801
Eth
0.718
VLPO
0.713
VMPO
0.712
SPA
0.648
AVPV
0.648
TU
0.638
TMv
0.621
MD
0.602
PD
0.579

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.391
Top-region fraction
0.116
Filter status
PASS

Interpretation limits