Abstract
Neurodevelopmental disorders that cause cognitive, behavioural or motor impairments affect around 15% of children and adolescents worldwide1, with diagnoses of profound autism and attention deficit hyperactivity disorder increasing in the USA and contributing to a major economic burden2,3. Yet the origins and mechanisms of these conditions remain poorly understood, limiting progress in therapies. Comprehensive cell atlases of the developing human brain, alongside those of model organisms such as mice and non-human primates, are now providing high-resolution measures of gene expression, cell-type abundance and spatial distribution. In this Perspective, we highlight recent studies that have identified novel developmental cell populations, revealed conserved and divergent patterns of cell genesis, migration and maturation across species, and begun testing hypotheses that link them to processes ranging from transcriptional control of cell fate specification to the emergence of complex behaviours. We present remaining conceptual and technical challenges and provide an outlook on how further studies of human and mammalian brain development can empower a deeper understanding of neurodevelopmental and neuropsychiatric disorders. Future efforts expanding to additional developmental stages, including adolescence, as well as whole-brain, multimodal and cross-species integration, will yield new insights into how development shapes the brain. These atlases promise to serve as essential references for unravelling mechanisms of brain function and disease vulnerability, and for advancing precision medicine.
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Acknowledgements
The research was funded by the US National Institutes of Health (NIH) under grant numbers U19MH114830 and U01MH130962 (to H.Z.); R01NS123263 and R01MH128364 (to T.J.N.); R00NS111731 and R01MH132689 (to A.B.); RF1MH124605 (to Y.K.); K99MH131832 (to L.W.); UM1MH130991 (to A.R.K., N.S. and A.B); R01MH134981 and DP2MH122400 (to A.A.P.); UM1HG011585, U19MH114821, R01HD082131 and R01NS112399 (to C.D.); UM1MH130981 and DP2MH140136 (to F.M.K.); RF1MH128876 (to R.F.); R01MH113005 and R01LM012736 (to J.G. and J.M.W.); and R24MH114788 and R24MH114815 (to S.A.A. and C.C.). H.Z., Z.Y., C.T.J.v.V., X.C. and Y.G. were also supported by the Allen Institute. This research was also supported by California Institute for Regenerative Medicine DISC0-14429, as well as gifts to T.J.N. from the Esther A. & Joseph Klingenstein Fund, the Shurl and Kay Curci Foundation, the Sontag Foundation, and the William K. Bowes Jr Foundation. T.J.N. is a New York Stem Cell Foundation Robertson Neuroscience Investigator, and A.A.P. is a New York Stem Cell Foundation Robertson Stem Cell Investigator. This research was also supported by the Alfred P. Sloan Foundation, the Rose Hills Foundation, a Klingenstein-Simons Fellowship and an Ablon Scholar Award to A.B.; W. M. Keck Foundation and Pershing Foundation awards to A.A.P.; and a Klingenstein-Simons Fellowship to F.M.K. This research was also supported by Jane Coffin Childs Medical Research Award grant 61-1749 to H.S.K., and a NOMIS Foundation Award and the Howard Hughes Medical Institute to C.D. J.M.W. was supported by National Science Foundation award DGE-1938105, and E.K.C. was supported by National Science Foundation grant GRFP 2034836. S.V. and J.L.W. were Schmidt Science Fellows, and J.L.W. was also a Jane Coffin Childs Fellow.
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T.J.N., P.R.N., A.B. and H.Z. led the writing with inputs and editing from all authors (T.J.N., P.R.N., K.S.M., X.C., E.K.C., W.D., Y.G., M.H., J.J., H.S.K., F.N.K., R.K., C.C.A.M., M.S., M.R.S., S.V., J.L.W., L.W., J.M.W., D.Z., G.Y., G.Z., S.A.A., C.C., C.D., R.F., J.G., A.R.K., F.M.K., Y.K., S.L., P.P.M., A.A.P., N.S., D.J.T., C.T.J.v.V., Z.Y., A.B. and H.Z.). C.T.J.v.V., J.L.W., T.J.N., A.A.P., N.S., A.B. and H.Z. prepared figures. K.S.M. coordinated the study. T.J.N., A.B. and H.Z. supervised the study.
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H.Z. is on the scientific advisory board of MapLight Therapeutics. N.S. is a co-founder and board member of Bexorg. A.R.K. is a co-founder of and consultant to Neurona Therapeutics.
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Nowakowski, T.J., Nano, P.R., Matho, K.S. et al. The new frontier in understanding human and mammalian brain development. Nature 647, 51–59 (2025). https://doi.org/10.1038/s41586-025-09652-1
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DOI: https://doi.org/10.1038/s41586-025-09652-1
