02271nas a2200301   4500000000100000000000100001008004100002260001200043653001200055653002500067653001000092653002900102653001100131653002200142653001700164653001200181653002500193653001700218100002300235700002100258700002500279700002600304245007600330300001200406490000800418520152900426022001401955       2024                            d  c2024-0610aAnimals10aBiological Evolution10aBrain10aGene Regulatory Networks10aHumans10aNeural Stem Cells10aNeurogenesis10aNeurons10aSingle-Cell Analysis10aTime Factors1 aFeline W. Lindhout1 aFenna M. Krienen1 aKatherine S. Pollard1 aMadeline A. Lancaster00aA molecular and cellular perspective on human brain evolution and tempo  a596-6080 v6303 aThe evolution of the modern human brain was accompanied by distinct molecular and cellular specializations, which underpin our diverse cognitive abilities but also increase our susceptibility to neurological diseases. These features, some specific to humans and others shared with related species, manifest during different stages of brain development. In this multi-stage process, neural stem cells proliferate to produce a large and diverse progenitor pool, giving rise to excitatory or inhibitory neurons that integrate into circuits during further maturation. This process unfolds over varying time scales across species and has progressively become slower in the human lineage, with differences in tempo correlating with differences in brain size, cell number and diversity, and connectivity. Here we introduce the terms 'bradychrony' and 'tachycrony' to describe slowed and accelerated developmental tempos, respectively. We review how recent technical advances across disciplines, including advanced engineering of in vitro models, functional comparative genetics and high-throughput single-cell profiling, are leading to a deeper understanding of how specializations of the human brain arise during bradychronic neurodevelopment. Emerging insights point to a central role for genetics, gene-regulatory networks, cellular innovations and developmental tempo, which together contribute to the establishment of human specializations during various stages of neurodevelopment and at different points in evolution.  a1476-4687