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| Home > Publications database > Topographic Axes of Wiring Space Converge to Genetic Topography in Shaping Human Cortical Layout |
| Home > Publications database > Topographic Axes of Wiring Space Converge to Genetic Topography in Shaping Human Cortical Layout |
| Journal Article | FZJ-2025-00817 |
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2025
Soc.
Washington, DC
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Please use a persistent id in citations: doi:10.1523/JNEUROSCI.1510-24.2024 doi:10.34734/FZJ-2025-00817
Abstract: Genetic information is involved in the gradual emergence of cortical areas since the neural tube begins to form, shaping the heterogeneous functions of neural circuits in the human brain. Informed by invasive tract-tracing measurements, the cortex exhibits marked interareal variation in connectivity profiles, revealing the heterogeneity across cortical areas. However, it remains unclear about the organizing principles possibly shared by genetics and cortical wiring to manifest the spatial heterogeneity across cortex. Instead of considering a complex one-to-one mapping between genetic coding and interareal connectivity, we hypothesized the existence of a more efficient way that the organizing principles are embedded in genetic profiles to underpin the cortical wiring space. Leveraging vertex-wise tractography in diffusion-weighted MRI, we derived the global connectopies in both female and male to reliably index the organizing principles of interareal connectivity variation in a low-dimensional space, which captured three dominant topographic patterns along the dorsoventral, rostrocaudal, and mediolateral axes of the cortex. More importantly, we demonstrated that the global connectopies converge with the gradients of a vertex-by-vertex genetic correlation matrix on the phenotype of cortical morphology and the cortex-wide spatiomolecular gradients. By diving into the genetic profiles, we found that the critical role of genes scaffolding the global connectopies was related to brain morphogenesis and enriched in radial glial cells before birth and excitatory neurons after birth. Taken together, our findings demonstrated the existence of a genetically determined space that encodes the interareal connectivity variation, which may give new insights into the links between cortical connections and arealization.Significance Statement Genetic factors have involved the gradual emergence of cortical areas since the neural tube begins to form, shaping the specialization of neural circuitry in the human brain. However, the mechanisms through which genetics encode the complex interareal connectivity remain a pivotal and unanswered question in the field of neuroscience. Here, we hypothesized that a genetically determined space encoding the interareal connectivity variation exists, which may give new insights into the links between cortical connections and arealization. We combined diffusion tractography with a dimension reduction framework to unravel the underlying global topographic principle revealed by the anatomical connections.
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