Deciphering the functional specialization of whole-brain spatiomolecular gradients in the adult brain
(2024) In Proceedings of the National Academy of Sciences of the United States of America 121(25). p.1-12- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2024-06-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Proceedings of the National Academy of Sciences of the United States of America
- volume
- 121
- issue
- 25
- pages
- 12 pages
- publisher
- National Academy of Sciences
- external identifiers
-
- pmid:38861593
- scopus:85195888008
- ISSN
- 0027-8424
- DOI
- 10.1073/pnas.2219137121
- language
- English
- LU publication?
- yes
- id
- 7e17ad7b-39c0-41bc-b39b-4f9da59c5df2
- date added to LUP
- 2024-08-20 13:58:27
- date last changed
- 2024-09-03 16:27:08
@article{7e17ad7b-39c0-41bc-b39b-4f9da59c5df2,
abstract = {{<p>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.</p>}},
author = {{Vogel, Jacob W. and Alexander-Bloch, Aaron F. and Wagstyl, Konrad and Bertolero, Maxwell A. and Markello, Ross D. and Pines, Adam and Sydnor, Valerie J. and Diaz-Papkovich, Alex and Hansen, Justine Y. and Evans, Alan C. and Bernhardt, Boris and Misic, Bratislav and Satterthwaite, Theodore D. and Seidlitz, Jakob}},
issn = {{0027-8424}},
language = {{eng}},
month = {{06}},
number = {{25}},
pages = {{1--12}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences of the United States of America}},
title = {{Deciphering the functional specialization of whole-brain spatiomolecular gradients in the adult brain}},
url = {{http://dx.doi.org/10.1073/pnas.2219137121}},
doi = {{10.1073/pnas.2219137121}},
volume = {{121}},
year = {{2024}},
}