A diffusion MRI-based spatiotemporal continuum of the embryonic mouse brain for probing gene-neuroanatomy connections Journal Article


Authors: Wu, D.; Richards, L. J.; Zhao, Z.; Cao, Z.; Luo, W.; Shao, W.; Shi, S. H.; Miller, M. I.; Mori, S.; Blackshaw, S.; Zhang, J.
Article Title: A diffusion MRI-based spatiotemporal continuum of the embryonic mouse brain for probing gene-neuroanatomy connections
Abstract: The embryonic mouse brain undergoes drastic changes in establishing basic anatomical compartments and laying out major axonal connections of the developing brain. Correlating anatomical changes with gene-expression patterns is an essential step toward understanding the mechanisms regulating brain development. Traditionally, this is done in a cross-sectional manner, but the dynamic nature of development calls for probing gene-neuroanatomy interactions in a combined spatiotemporal domain. Here, we present a four-dimensional (4D) spatiotemporal continuum of the embryonic mouse brain from E10.5 to E15.5 reconstructed from diffusion magnetic resonance microscopy (dMRM) data. This study achieved unprecedented high-definition dMRM at 30- to 35-μm isotropic resolution, and together with computational neuroanatomy techniques, we revealed both morphological and microscopic changes in the developing brain. We transformed selected gene-expression data to this continuum and correlated them with the dMRM-based neuroanatomical changes in embryonic brains. Within the continuum, we identified distinct developmental modes comprising regional clusters that shared developmental trajectories and similar gene-expression profiles. Our results demonstrate how this 4D continuum can be used to examine spatiotemporal gene-neuroanatomical interactions by connecting upstream genetic events with anatomical changes that emerge later in development. This approach would be useful for large-scale analysis of the cooperative roles of key genes in shaping the developing brain. Copyright © 2022 the Author(s). Published by PNAS.
Keywords: controlled study; microscopy; nonhuman; mouse; gene expression; embryo; animal experiment; brain; diffusion weighted imaging; neuroanatomy; male; article; developmental mode; diffusion mr microscopy; embryonic mouse brain; spatiotemporal continuum
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 119
Issue: 7
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2022-02-15
Start Page: e2111869119
Language: English
DOI: 10.1073/pnas.2111869119
PUBMED: 35165149
PROVIDER: scopus
PMCID: PMC8851557
DOI/URL:
Notes: Article -- Export Date: 1 March 2022 -- Source: Scopus
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  1. Song-Hai Shi
    52 Shi
  2. Wei   Shao
    6 Shao