Yuan W, Ma S, Brown JR, Kim K, Murek V, Trastulla L, Meissner A, Lodato S, Shetty AS, Levin JZ, Buenrostro JD, Ziller MJ, Arlotta P. 2022. Temporally divergent regulatory mechanisms govern neuronal diversification and maturation in the mouse and marmoset neocortex. Nature neuroscience. 25(8):1049-1058. Pubmed: 35915179 DOI:10.1038/s41593-022-01123-4


Mammalian neocortical neurons span one of the most diverse cell type spectra of any tissue. Cortical neurons are born during embryonic development, and their maturation extends into postnatal life. The regulatory strategies underlying progressive neuronal development and maturation remain unclear. Here we present an integrated single-cell epigenomic and transcriptional analysis of individual mouse and marmoset cortical neuron classes, spanning both early postmitotic stages of identity acquisition and later stages of neuronal plasticity and circuit integration. We found that, in both species, the regulatory strategies controlling early and late stages of pan-neuronal development diverge. Early postmitotic neurons use more widely shared and evolutionarily conserved molecular regulatory programs. In contrast, programs active during later neuronal maturation are more brain- and neuron-specific and more evolutionarily divergent. Our work uncovers a temporal shift in regulatory choices during neuronal diversification and maturation in both mice and marmosets, which likely reflects unique evolutionary constraints on distinct events of neuronal development in the neocortex.
© 2022. The Author(s).

Related Faculty

Photo of Jason Buenrostro

The Buenrostro lab is broadly dedicated to advancing our knowledge of gene regulation and the downstream consequences on cell fate decisions.

Photo of Paola Arlotta

Dr. Arlotta is interested in understanding the molecular laws that govern the birth, differentiation and assembly of the cerebral cortex, the part of the brain that controls how we sense, move and think. She integrates developmental and evolutionary knowledge to investigate therapies for brain repair and for modeling neuropsychiatric disease.

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