A comprehensive transcriptional map of primate brain development.
Bakken TE., Miller JA., Ding S-L., Sunkin SM., Smith KA., Ng L., Szafer A., Dalley RA., Royall JJ., Lemon T., Shapouri S., Aiona K., Arnold J., Bennett JL., Bertagnolli D., Bickley K., Boe A., Brouner K., Butler S., Byrnes E., Caldejon S., Carey A., Cate S., Chapin M., Chen J., Dee N., Desta T., Dolbeare TA., Dotson N., Ebbert A., Fulfs E., Gee G., Gilbert TL., Goldy J., Gourley L., Gregor B., Gu G., Hall J., Haradon Z., Haynor DR., Hejazinia N., Hoerder-Suabedissen A., Howard R., Jochim J., Kinnunen M., Kriedberg A., Kuan CL., Lau C., Lee C-K., Lee F., Luong L., Mastan N., May R., Melchor J., Mosqueda N., Mott E., Ngo K., Nyhus J., Oldre A., Olson E., Parente J., Parker PD., Parry S., Pendergraft J., Potekhina L., Reding M., Riley ZL., Roberts T., Rogers B., Roll K., Rosen D., Sandman D., Sarreal M., Shapovalova N., Shi S., Sjoquist N., Sodt AJ., Townsend R., Velasquez L., Wagley U., Wakeman WB., White C., Bennett C., Wu J., Young R., Youngstrom BL., Wohnoutka P., Gibbs RA., Rogers J., Hohmann JG., Hawrylycz MJ., Hevner RF., Molnár Z., Phillips JW., Dang C., Jones AR., Amaral DG., Bernard A., Lein ES.
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.