Dependence on the transcription factor Shox2 for specification of sensory neurons conveying discriminative touch
Bibliographic record
Abstract
Touch sensation is mediated by specific subtypes of sensory neurons which develop in a hierarchical process from common early progenitor neurons, but the molecular mechanism that underlies diversification of touch-sensitive mechanoreceptive neurons is not fully known. Here, we use genetically manipulated mice to examine whether the transcription factor short stature homeobox 2 (Shox2) participates in the acquisition of neuronal subtypes conveying touch sensation. We show that Shox2 encodes the development of category I low-threshold mechanoreceptive neurons in glabrous skin, i.e. discriminative touch-sensitive neurons which form innervations of epidermal Merkel cell and Meissner corpuscles. In contrast, other sensory fiber endings, including those innervating Pacinian corpuscles, are not dependent on Shox2. Shox2 is expressed in neurons of most or all classes of sensory neurons at early embryonic stages and is later confined to touch-sensitive neurons expressing Ret and/or TrkB. Conditional deletion of Shox2 and analysis of Runx3(-/-);Bax(-/-) mutant mice reveals that Runx3 is suppressing Shox2 while Shox2 is necessary for TrkB expression, and that these interactions are necessary for diversification of TrkB(+) and TrkC(+) mechanoreceptive neurons. In particular, development of TrkB(+)/Ret(+) and TrkB(+)/Ret(-) touch-sensitive neurons is critically dependent on Shox2. Consistently, Shox2 conditional mutant mice demonstrate a dramatic impairment of light touch responses. These results show that Shox2 is required for specification of a subclass of TrkB(+) sensory neurons which convey the sensation of discriminative touch arising from stimuli of the skin.
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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) | 0.000 | 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 | 0.001 |
| 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".