Genetics of mirror movements identifies a multifunctional complex required for Netrin-1 guidance and lateralization of motor control
Bibliographic record
Abstract
Mirror movements (MM) disorder is characterized by involuntary movements on one side of the body that mirror intentional movements on the opposite side. We performed genetic characterization of a family with autosomal dominant MM and identified ARHGEF7 , a RhoGEF, as a candidate MM gene. We found that Arhgef7 and its partner Git1 bind directly to Dcc. Dcc is the receptor for Netrin-1, an axon guidance cue that attracts commissural axons to the midline, promoting the midline crossing of axon tracts. We show that Arhgef7 and Git1 are required for Netrin-1–mediated axon guidance and act as a multifunctional effector complex. Arhgef7/Git1 activates Rac1 and Cdc42 and inhibits Arf1 downstream of Netrin-1. Furthermore, Arhgef7/Git1, via Arf1, mediates the Netrin-1–induced increase in cell surface Dcc. Mice heterozygous for Arhgef7 have defects in commissural axon trajectories and increased symmetrical paw placements during skilled walking, a MM-like phenotype. Thus, we have delineated how ARHGEF7 mutation causes MM.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".