Molecular architecture of the developing mouse brain

Gioele La Manno (), Kimberly Siletti, Alessandro Furlan, Daniel Gyllborg, Elin Vinsland, Alejandro Mossi Albiach, Christoffer Mattsson Langseth, Irina Khven, Alex R. Lederer, Lisa M. Dratva, Anna Johnsson, Mats Nilsson, Peter Lönnerberg and Sten Linnarsson ()
Additional contact information
Gioele La Manno: Karolinska Institute
Kimberly Siletti: Karolinska Institute
Alessandro Furlan: Karolinska Institute
Daniel Gyllborg: Stockholm University
Elin Vinsland: Karolinska Institute
Alejandro Mossi Albiach: Karolinska Institute
Christoffer Mattsson Langseth: Stockholm University
Irina Khven: École Polytechnique Fédérale de Lausanne
Alex R. Lederer: École Polytechnique Fédérale de Lausanne
Lisa M. Dratva: École Polytechnique Fédérale de Lausanne
Anna Johnsson: Karolinska Institute
Mats Nilsson: Stockholm University
Peter Lönnerberg: Karolinska Institute
Sten Linnarsson: Karolinska Institute

Nature, 2021, vol. 596, issue 7870, 92-96

Abstract: Abstract The mammalian brain develops through a complex interplay of spatial cues generated by diffusible morphogens, cell–cell interactions and intrinsic genetic programs that result in probably more than a thousand distinct cell types. A complete understanding of this process requires a systematic characterization of cell states over the entire spatiotemporal range of brain development. The ability of single-cell RNA sequencing and spatial transcriptomics to reveal the molecular heterogeneity of complex tissues has therefore been particularly powerful in the nervous system. Previous studies have explored development in specific brain regions1–8, the whole adult brain9 and even entire embryos10. Here we report a comprehensive single-cell transcriptomic atlas of the embryonic mouse brain between gastrulation and birth. We identified almost eight hundred cellular states that describe a developmental program for the functional elements of the brain and its enclosing membranes, including the early neuroepithelium, region-specific secondary organizers, and both neurogenic and gliogenic progenitors. We also used in situ mRNA sequencing to map the spatial expression patterns of key developmental genes. Integrating the in situ data with our single-cell clusters revealed the precise spatial organization of neural progenitors during the patterning of the nervous system.

Date: 2021
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DOI: 10.1038/s41586-021-03775-x

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