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Nature. 2016 Jul 21;535(7612):367-75. doi: 10.1038/nature18637.

A comprehensive transcriptional map of primate brain development.

Author information

1
Allen Institute for Brain Science, Seattle, Washington 98109, USA.
2
Department of Psychiatry and Behavioral Science, California National Primate Research Center, The M.I.N.D. Institute, University of California, Davis, Sacramento, California 95817, USA.
3
Department of Radiology, University of Washington, Seattle, Washington 98195, USA.
4
Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
5
Human Genome Sequencing Center and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
6
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington 98101, USA.

Abstract

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like molecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental timing of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, although approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny compared to monkey.

PMID:
27409810
PMCID:
PMC5325728
DOI:
10.1038/nature18637
[Indexed for MEDLINE]
Free PMC Article
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