Deciphering the functional specialization of whole-brain spatiomolecular gradients in the adult brain.

Autor:	Vogel JW; Department of Clinical Sciences Malmö, SciLifeLab, Lund University, Lund, Sweden 202 13.; Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA 19104.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104., Alexander-Bloch AF; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104.; Department of Child and Adolescent Psychiatry and Behavioral Science, The Children's Hospital of Philadelphia, Philadelphia, PA 19104.; Penn-Children's Hospital of Philadelphia Lifespan Brain Institute, University of Pennsylvania, Philadelphia, PA 19104., Wagstyl K; Wellcome Centre for Human Neuroimaging, Institute of Neurology, University College London, London WC1N 3AR, United Kingdom., Bertolero MA; Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA 19104.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104., Markello RD; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada., Pines A; Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA 19104.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104.; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305., Sydnor VJ; Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA 19104.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104., Diaz-Papkovich A; Quantitative Life Sciences, McGill University, Montreal, QC H3A 1E3, Canada.; McGill Genome Centre, McGill University, Montreal, QC H3A 0G1, Canada., Hansen JY; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada., Evans AC; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada., Bernhardt B; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada., Misic B; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada., Satterthwaite TD; Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA 19104.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104.; Penn-Children's Hospital of Philadelphia Lifespan Brain Institute, University of Pennsylvania, Philadelphia, PA 19104., Seidlitz J; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104.; Department of Child and Adolescent Psychiatry and Behavioral Science, The Children's Hospital of Philadelphia, Philadelphia, PA 19104.; Penn-Children's Hospital of Philadelphia Lifespan Brain Institute, University of Pennsylvania, Philadelphia, PA 19104.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jun 18; Vol. 121 (25), pp. e2219137121. Date of Electronic Publication: 2024 Jun 11.
DOI:	10.1073/pnas.2219137121
Abstrakt:	Cortical arealization arises during neurodevelopment from the confluence of molecular gradients representing patterned expression of morphogens and transcription factors. However, whether similar gradients are maintained in the adult brain remains unknown. Here, we uncover three axes of topographic variation in gene expression in the adult human brain that specifically capture previously identified rostral-caudal, dorsal-ventral, and medial-lateral axes of early developmental patterning. The interaction of these spatiomolecular gradients i) accurately reconstructs the position of brain tissue samples, ii) delineates known functional territories, and iii) can model the topographical variation of diverse cortical features. The spatiomolecular gradients are distinct from canonical cortical axes differentiating the primary sensory cortex from the association cortex, but radiate in parallel with the axes traversed by local field potentials along the cortex. We replicate all three molecular gradients in three independent human datasets as well as two nonhuman primate datasets and find that each gradient shows a distinct developmental trajectory across the lifespan. The gradients are composed of several well-known transcription factors (e.g., PAX6 and SIX3 ), and a small set of genes shared across gradients are strongly enriched for multiple diseases. Together, these results provide insight into the developmental sculpting of functionally distinct brain regions, governed by three robust transcriptomic axes embedded within brain parenchyma. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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