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

Author:

Wu Dan123ORCID,Richards Linda J.4,Zhao Zhiyong1ORCID,Cao Zuozhen1,Luo Wanrong1,Shao Wei5,Shi Song-Hai56,Miller Michael I.789,Mori Susumu1011,Blackshaw Seth1213141516ORCID,Zhang Jiangyang17ORCID

Affiliation:

1. Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310027, China

2. Department of Neurology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China

3. Binjiang Institute of Zhejiang University, Hangzhou 310053, China

4. McDonnell Center for Cellular & Molecular Neurobiology, Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110

5. Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065

6. International Data Group (IDG)/McGovern Institute for Brain Research, Tsinghua-Peking Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China

7. Department of Biomedicine Engineering, Johns Hopkins University, Baltimore, MD 21218

8. Center of Imaging Science, Johns Hopkins University, Baltimore, MD 21218

9. Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21218

10. Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205

11. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205

12. Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205

13. Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205

14. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205

15. Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205

16. Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205

17. Department of Radiology, NYU Langone School of Medicine, New York, NY 10016

Abstract

Significance We established an ultra high-resolution diffusion MRI atlas of the embryonic mouse brains from E10.5 to E15.5, which characterizes the continuous changes of brain morphology and microstructures at mesoscopic scale. By integrating gene-expression data into the spatiotemporal continuum, we can navigate the evolving landscape of gene expression and neuroanatomy across both spatial and temporal dimensions to visualize their interactions in normal and abnormal embryonic brain development. We also identified regional clusters with distinct developmental trajectories and identified gene-expression profiles that matched to these regional domains. The diffusion MRI–based continuum of the embryonic brain and the computational techniques presented in this study offer a valuable tool for systematic study of the genetic control of brain development.

Funder

Ministry of Science and Technology of the People''''s Republic of China

National Natural Science Foundation of China

HHS | NIH | National Institute of Neurological Disorders and Stroke

HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development

Science and Technology Department of Zhejiang Province

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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