Fzd9

Frizzled-9 (Fz-9) (mFz3) (mFz9) (CD antigen CD349)

Spatial tier: RESTRICTED · Class: GPCR · Top region: AD (Anterodorsal nucleus) · Positive regions: 25/554

43.2Discovery Score
37.2Targetability Score
CEvidence grade C
What this means: Fzd9: fine CCF profile is restricted toward AD (top regions: AD, V, MH, VCO, SNc; 25 positive regions); direct spatial validation is still required.

Function in AD: evidence, prediction, innovation

Gene function
Fzd9 encodes Frizzled-9, a seven-transmembrane Wnt receptor. It is activated by Wnt-2 and signals through the canonical Wnt/beta-catenin pathway, and also influences cytoskeletal dynamics and receptor clustering. In humans it lies within the Williams syndrome deletion interval on chromosome 7q11.23.
Region function
The anterodorsal thalamic nucleus relays vestibular head-direction information to postsubiculum and entorhinal cortex and is required for stable spatial orientation and normal hippocampal-dependent spatial memory.
Published in this region
inferred No region-specific literature found. Frizzled-9 is described as selectively expressed in hippocampus, where null mice show increased dentate gyrus apoptosis, fewer granule cells, lowered seizure thresholds and severe visuospatial learning deficits (Zhao et al. 2005); its canonical activation by Wnt-2 was shown by Karasawa et al. 2002.
Predicted function
Prediction: in AD, Frizzled-9 would most plausibly act developmentally, setting thalamic neuron survival and anterior-thalamic axon targeting to postsubiculum and entorhinal cortex via Wnt/beta-catenin, as it does in dentate gyrus. Thalamus-restricted deletion should give a smaller AD with mistargeted projections and a spatial-orientation deficit dissociable from hippocampal pathology. Fzd9 haploinsufficiency also contributes to the Williams syndrome visuospatial phenotype.
Innovation
★★★★☆ 4/5 Fzd9 work has focused almost entirely on hippocampus, leaving a plausible and clinically relevant thalamic head-direction role unexamined.
Tools
Fzd9 null mice (Zhao et al. 2005); Wnt-2 ligand and modulators XAV939 and CHIR99021; anti-FZD9 antibodies; thalamic targeting via Gbx2-CreER or Rorb/Calb2 drivers with AAV.
References

Direct evidence located at the region

Fzd9 Allen ISH at the CCF centroid of AD

Allen ISH experiment 73907498, section image 73846723 (section 293): the section that contains the CCF centroid of Anterodorsal 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

Look it up yourself: Allen Mouse Brain ISH for Fzd9Allen reference atlas: AD (structure 64)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Fzd9" or by parcellation_substructure "AD")All genes confined to AD + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
AD MERFISH region locator
Real single-cell MERFISH coordinates for the AD (Anterodorsal 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.

Regional expression figure

Fzd9 regional expression profile

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

Spatial profile

AD
0.996
V
0.875
MH
0.815
VCO
0.698
SNc
0.624
MT
0.545
I5
0.544
SPVO
0.525
LRNp
0.509
CM
0.497
y
0.496
PF
0.492
NTB
0.49
SNr
0.488
VTA
0.485
LAV
0.481
P5
0.478
VI
0.458
IP
0.457
B
0.454

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.293
Top-region fraction
0.056
Filter status
PASS

Interpretation limits