FIBCD1 is a Conserved Receptor for Chondroitin Sulphate Proteoglycans of the Brain Extracellular Matrix and a Candidate Gene for a Complex Neurodevelopmental Disorder
Bibliographic record
Abstract
ABSTRACT The brain extracellular matrix (ECM) is enriched in chondroitin sulphate proteoglycans (CSPGs) with variable sulphate modifications that intimately participate in brain maturation and function. Very little is known about how the changing biophysical properties of the CSPGs are signalled to neurons. Here, we report Fibrinogen C Domain Containing 1 (FIBCD1), a known chitin-binding receptor of the innate immune system, to be highly expressed in the hippocampus and to specifically bind CSPGs containing 4-O sulphate modification (CS-4S). Cultured Fibcd1 knockout (KO) neurons lack phenotypic and transcriptomic responses to CSPG stimulation. Further, Fibcd1 KO mice exhibit accumulation of CS-4S, likely resulting in deficits of hippocampal-dependent learning tasks and abrogated synaptic remodelling, a phenotype rescued by enzymatic digestion of CSPGs. Likewise, neuronal specific knockdown of a Fibcd1 orthologue in flies results in neuronal morphological changes at the neuromuscular junctions and behavioural defects. Finally, we report two undiagnosed patients with a complex neurodevelopmental disorder with deleterious variants in FIBCD1, strongly implicating FIBCD1 in the development of the disease. Taken together, our results demonstrate that FIBCD1 is a novel, evolutionarily conserved component of ECM sulphation recognition that is crucial for neuronal development and function.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".