The Small, Secreted Immunoglobulin Protein ZIG-3 Maintains Axon Position in <i>Caenorhabditis elegans</i>
Bibliographic record
Abstract
Vertebrate and invertebrate genomes contain scores of small secreted or transmembrane proteins with two immunoglobulin (Ig) domains. Many of them are expressed in the nervous system, yet their function is not well understood. We analyze here knockout alleles of all eight members of a family of small secreted or transmembrane Ig domain proteins, encoded by the Caenorhabditis elegans zig ("zwei Ig Domänen") genes. Most of these family members display the unusual feature of being coexpressed in a single neuron, PVT, whose axon is located along the ventral midline of C. elegans. One of these genes, zig-4, has previously been found to be required for maintaining axon position postembryonically in the ventral nerve cord of C. elegans. We show here that loss of zig-3 function results in similar postdevelopmental axon maintenance defects. The maintenance function of both zig-3 and zig-4 serves to counteract mechanical forces that push axons around, as well as various intrinsic attractive forces between axons that cause axon displacement if zig genes like zig-3 or zig-4 are deleted. Even though zig-3 is expressed only in a limited number of neurons, including PVT, transgenic rescue experiments show that zig-3 can function irrespective of which cell or tissue type it is expressed in. Double mutant analysis shows that zig-3 and zig-4 act together to affect axon maintenance, yet they are not functionally interchangeable. Both genes also act together with other, previously described axon maintenance factors, such as the Ig domain proteins DIG-1 and SAX-7, the C. elegans ortholog of the human L1 protein. Our studies shed further light on the use of dedicated factors to maintain nervous system architecture and corroborate the complexity of the mechanisms involved.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".