18w (18 wheeler, Toll-2, A1ZBR2) — review notes

Batch 1 (Toll/TLR axis) of the INNATE_IMMUNITY project. Falcon deep research had not
started for this gene when the review was drafted; notes are built from the cached
GOA publications and the UniProt record.

Identity

• Toll family LRR-TM-TIR receptor, also called Toll-2 PMID:7600965.
• No ligand has been identified. Spätzle-1 did not activate Toll-2 in S2 cells PMID:31088910.

Developmental roles (core)

• Morphogenesis / adhesion PMID:7600965.
• Convergent extension: with Toll-6 and Toll-8 forms a positional code PMID:25363762.
• Follicle cell migration and eggshell shape PMID:16607637.
• CNS: an 18w allele was recovered in an Ap4/FMRFa specification screen PMID:26092715.

Immunity: not a PRR, adult role dispensable

• Original proposal PMID:9321392.
• Re-evaluation PMID:12101100.
• A Toll-ectodomain/18W-TIR chimera did not induce drosomycin PMID:10973475, whereas an isolated overexpressed 18W TIR modestly did PMID:31088910.
• Project question 1: no PRR (GO:0038187) or GO:0002224 annotation on 18w. Its immune annotations (antibacterial humoral response IMP; immune response IEP) are best read as secondary to the larval fat-body developmental defect; marked over-annotated. The GOA NOT annotation (antimicrobial humoral response) is supported and accepted.

Falcon deep research (added after it completed)

• The Falcon report (file:DROME/18w/18w-deep-research-falcon.md) agrees on the immune phenotype: ["The immune phenotype is therefore best interpreted as secondary to defective tissue development rather than direct microbial recognition."]. This supports MARK_AS_OVER_ANNOTATED for the antibacterial humoral response and immune response rows.
• It reports a 2025 study (Alshamsi et al.) in which DNT-2/Spätzle-5 acts genetically through Toll-2 in visual-system neuron survival and targeting. Direct binding was not shown, and the paper was not cached or PMID-resolved in this session, so it is not cited in the review. It is a candidate for a future neurotrophin-receptor annotation. The report also mentions roles in salivary gland invagination and tracheal expression.