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Researchers developed a screening method to identify genes whose expression patterns mirror the anatomical organization of brain pathways. Testing 10,262 genes, they identified a 19-gene panel whose expression similarity across brain regions follows the sequential order of the dorsal column-medial lemniscus pathway, a major somatosensory route from spinal cord through brainstem and thalamus to cortex. The panel's regional similarity pattern significantly outperformed randomly selected gene sets and showed consistent ordering across six human brain donors.
Why it matters
This work demonstrates that transcriptomic profiles can preserve anatomical pathway organization, potentially enabling molecular characterization of neural circuits. The approach could help validate pathway connectivity in human tissue samples and identify molecular signatures of specific neural systems for diagnostic or research purposes.
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⚠️ Preprint – Noch nicht peer-reviewed
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Neuroanatomical pathways link specialized brain regions, but whether regional transcriptomic profiles preserve relationships aligned with pathway order remains unclear. We defined candidate pathways and their available tissue representations from neuroanatomical literature, then screened 10,262 genes in the Body Index of Gene Expression (BIGE), a human microarray resource covering cells and tissues. The screen required expression across every mapped region of a route and limited single-region dominance. It identified 23 candidates in three routes with sufficient coverage; 19 met the criteria for the dorsal column-medial lemniscus (DCML) representation and formed the fixed panel. We evaluated this panel in six Allen Human Brain Atlas (AHBA) donors across three central regional representations: an aggregate of samples assigned to the cuneate and gracile nuclei (Cu/Gr), the lateral group of nuclei, ventral division, within the dorsal thalamus (DTLv), and postcentral gyrus. The regional-order contrast compared the mean similarity of the pairs adjacent in the anatomical sequence, Cu/Gr-DTLv and DTLv-postcentral gyrus, with Cu/Gr-postcentral gyrus similarity. Both adjacent-in-order correlations were positive in all six donors; the contrast was positive in five and reached a mean of T = 0.345175 (exact sign test, P = 0.109375). The panel exceeded two distributions of 50,000 gene sets generated under comparable selection constraints (P = 0.027919 and P = 0.026579). In descriptive anatomical comparisons, it ranked third among 240 combinations and first among the target and all 16 single-region substitutions. All 50,000 one-probe-per-gene analyses retained T > 0, and broad neuronal-expression contrasts were positive in medulla, thalamus, and cortex. Spatial support depended on the null model, with stronger evidence under whole-donor surrogates (P = 0.003860) than under the primary within-compartment model (P = 0.051179). These findings identify a fixed gene panel whose regional similarity is aligned with the represented central order of the DCML system and define a specific hypothesis for prospective evaluation in an independent, anatomically resolved dataset.