Muscle-Derived BMP4 Regulates Morphology and Function of Endplates on Extrafusal and Intrafusal Muscle Fibers in Adult Mice
Bibliographic record
Abstract
Understanding factors contributing to neuromuscular junction (NMJ) stability postdevelopment will shed light on how this stability is lost during aging and in neuromuscular diseases. Previous work in Drosophila suggests that morphogens within the bone morphogenic protein (BMP) family are potential candidates because the BMP homolog, gbb , along with its receptor, wit , have key roles in NMJ structure, stability, and function. Whether BMPs have similar roles at vertebrate NMJs is currently unknown. To examine this question, we generated doxycycline-inducible, muscle-specific BMP4 null mice, referred to here as HSA Cre BMP4 fl/fl mice. Motor behavior tasks were examined pre- and postinduction while electrophysiological and morphological characteristics were examined 4 months later in mice of both sexes. Soleus muscles from HSA Cre BMP4 fl/fl mice had significantly reduced contractile force compared with wild-type (WT) littermates. Cross-sectional areas of type I, but not type IIa, muscle fibers were reduced. NMJs were also larger in HSA Cre BMP4 fl/fl muscles compared with controls due to a significant increase in acetylcholine receptor fragment number and distribution. HSA Cre BMP4 fl/fl NMJs displayed reduced amplitude and frequency of miniature endplate potentials (mEPPs), evoked EPP amplitude, and quantal content and had increased failure rates when stimulating at high frequencies. Behaviorally, HSA Cre BMP4 fl/fl mice performed increasingly worse over time on the rotarod after doxycycline administration compared with their WT littermates. Finally, muscle spindle structure and proprioceptive function were significantly compromised in HSA Cre BMP4 fl/fl mice. These results indicate that muscle-derived BMP4 regulates morphological and electrophysiological attributes of the NMJ in adult mice as well as the structure and function of muscle spindles.
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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 | 0.001 |
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".