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

Dan Wu, Linda J. Richards, Zhiyong Zhao, Zuozhen Cao, Wanrong Luo, Wei Shao, Song Hai Shi, Michael I. Miller, Susumu Mori, Seth Blackshaw, Jiangyang Zhang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish
Article numbere2111869119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Feb 15 2022


  • developmental mode
  • diffusion MR microscopy
  • embryonic mouse brain
  • gene expression
  • spatiotemporal continuum


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