RT Journal Article SR Electronic T1 Temporally-Divergent Regulatory Mechanisms Govern Neuronal Development and Diversification in the Neocortex JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.08.23.263434 DO 10.1101/2020.08.23.263434 A1 Wen Yuan A1 Sai Ma A1 Juliana R. Brown A1 Kwanho Kim A1 Vanessa Murek A1 Lucia Trastulla A1 Alexander Meissner A1 Simona Lodato A1 Ashwin Shetty A1 Joshua Z. Levin A1 Jason D. Buenrostro A1 Michael J. Ziller A1 Paola Arlotta YR 2020 UL http://biorxiv.org/content/early/2020/08/24/2020.08.23.263434.abstract AB Mammalian neocortical neurons span one of the most diverse cell type spectra of any tissue. The regulatory strategies that neurons use during progressive development and maturation remain unclear. We present an integrated single-cell epigenomic and transcriptional analysis of individual classes of neurons from both mouse and marmoset neocortex, sampled during both early postmitotic stages of identity acquisition and later stages of neuronal plasticity and circuit integration. We find that in both species, the regulatory strategies controlling these early and late stages diverge: early postmitotic neurons use molecular regulatory programs with broader tissue distribution and greater evolutionary conservation, while programs active during later neuronal maturation implement more brain- and neuron-specific mechanisms showing greater evolutionary divergence. The data uncovers a temporally-regulated shift in regulatory choices, likely reflecting unique evolutionary constraints on distinct events of neuronal development in the neocortex.Competing Interest StatementThe authors have declared no competing interest.