Abstract
Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions.
Highlights
The human brain is organized in a hierarchy of multiple substructures, whose cell composition and circuitry are believed to allow each substructure to carry out its distinct function
These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions
We found that almost all genes in the adult human brain bear a developmental ‘footprint’ which determines their areal expression-pattern based on the developmental ontology of brain regions, while at the same time their spatial expression pattern changes during life
Summary
The human brain is organized in a hierarchy of multiple substructures, whose cell composition and circuitry are believed to allow each substructure to carry out its distinct function. While physiological and histological differences and similarities between structures have been intensively studied [1,2,3,4], the molecular profiles giving rise to those differences are far from being understood. It is not known which principles govern the expression patterns of genes across the adult brain and what determines their spatial organization. The most posterior vesicle, the rombencephalon, forms two secondary vesicles as well, the metencephalon, and the myelencephalon These five vesicles are aligned along the rostral-caudal axis of the developing brain and establish the primary organization of the central nervous system (Fig 1A) [7]
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