A conserved transcriptional axis links cortical organization, developmental timing and autism-associated perturbations
- 1Institute of Biophysics, Chinese Academy of Science
Abstract
Much of our mechanistic understanding of cortical development and neurodevelopmental disorders comes from studies in mice, yet translating these insights to humans rests on a fundamental assumption: that the cortex is organized according to conserved principles across species. Here, by independently decomposing human and mouse cortical transcriptomes, we test this assumption and identify a shared organizational axis extending from limbic anterior ventral (AV) to primary sensory posterior dorsal (PD) cortex. This axis aligns with conserved variation in cell-type composition, thalamocortical connectivity, myelination and excitation-inhibition balance. Its spatial topology emerges by mid-gestation and is progressively refined while remaining stable in orientation across subsequent development. What varies systematically along the axis is developmental timing: AV-enriched genes preferentially retained earlier cortical-construction features and progressively decline after birth, whereas PD-enriched genes preferentially reflected later maturation processes and progressively increased, with developmental rates graded along the axis. Across genetically distinct autism mouse models, developmental dysregulation converged on this axis, following a shared pattern that generally intensified toward the PD pole. The same axis also organized genotype-specific patterns of cortical volume alteration, while human autism risk genes showed corresponding enrichment along this transcriptional coordinate. Overall, we identify a conserved transcriptional axis that links cortical architecture to developmental timing and organizes the heterogeneous cortical effects of autism-associated mutations.
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BibTeX
@misc{huang2026conserved,
title = {{A conserved transcriptional axis links cortical organization, developmental timing and autism-associated perturbations}},
author = {S. Huang and Y. Peng and X. Tian and C. Dong and T. Zhang and Y. Shi and A. Li},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.05.749572},
url = {https://www.biorxiv.org/content/10.64898/2026.09.05.749572v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A conserved transcriptional axis links cortical organization, developmental timing and autism-associated perturbations
AU - S. Huang
AU - Y. Peng
AU - X. Tian
AU - C. Dong
AU - T. Zhang
AU - Y. Shi
AU - A. Li
PY - 2026
DA - 2026/09/05
PB - bioRxiv
DO - 10.64898/2026.09.05.749572
UR - https://www.biorxiv.org/content/10.64898/2026.09.05.749572v1
AB - Much of our mechanistic understanding of cortical development and neurodevelopmental disorders comes from studies in mice, yet translating these insights to humans rests on a fundamental assumption: that the cortex is organized according to conserved principles across species. Here, by independently decomposing human and mouse cortical transcriptomes, we test this assumption and identify a shared organizational axis extending from limbic anterior ventral (AV) to primary sensory posterior dorsal (PD) cortex. This axis aligns with conserved variation in cell-type composition, thalamocortical connectivity, myelination and excitation-inhibition balance. Its spatial topology emerges by mid-gestation and is progressively refined while remaining stable in orientation across subsequent development. What varies systematically along the axis is developmental timing: AV-enriched genes preferentially retained earlier cortical-construction features and progressively decline after birth, whereas PD-enriched genes preferentially reflected later maturation processes and progressively increased, with developmental rates graded along the axis. Across genetically distinct autism mouse models, developmental dysregulation converged on this axis, following a shared pattern that generally intensified toward the PD pole. The same axis also organized genotype-specific patterns of cortical volume alteration, while human autism risk genes showed corresponding enrichment along this transcriptional coordinate. Overall, we identify a conserved transcriptional axis that links cortical architecture to developmental timing and organizes the heterogeneous cortical effects of autism-associated mutations.
ER -