Kronman Fae A, Liwang Josephine K, Betty Rebecca, Vanselow Daniel J, Wu Yuan-Ting, Tustison Nicholas J, Bhandiwad Ashwin, Manjila Steffy B, Minteer Jennifer A, Shin Donghui, Lee Choong Heon, Patil Rohan, Duda Jeffrey T, Puelles Luis, Gee James C, Zhang Jiangyang, Ng Lydia, Kim Yongsoo
Department of Neural and Behavioral Sciences, College of Medicine, The Pennsylvania State University, Hershey, PA.
Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA.
bioRxiv. 2023 Sep 15:2023.09.14.557789. doi: 10.1101/2023.09.14.557789.
3D standard reference brains serve as key resources to understand the spatial organization of the brain and promote interoperability across different studies. However, unlike the adult mouse brain, the lack of standard 3D reference atlases for developing mouse brains has hindered advancement of our understanding of brain development. Here, we present a multimodal 3D developmental common coordinate framework (DevCCF) spanning mouse embryonic day (E) 11.5, E13.5, E15.5, E18.5, and postnatal day (P) 4, P14, and P56 with anatomical segmentations defined by a developmental ontology. At each age, the DevCCF features undistorted morphologically averaged atlas templates created from Magnetic Resonance Imaging and co-registered high-resolution templates from light sheet fluorescence microscopy. Expert-curated 3D anatomical segmentations at each age adhere to an updated prosomeric model and can be explored via an interactive 3D web-visualizer. As a use case, we employed the DevCCF to unveil the emergence of GABAergic neurons in embryonic brains. Moreover, we integrated the Allen CCFv3 into the P56 template with stereotaxic coordinates and mapped spatial transcriptome cell-type data with the developmental ontology. In summary, the DevCCF is an openly accessible resource that can be used for large-scale data integration to gain a comprehensive understanding of brain development.
三维标准参考脑图谱是理解大脑空间组织以及促进不同研究之间互操作性的关键资源。然而,与成年小鼠大脑不同的是,发育中小鼠大脑缺乏标准的三维参考图谱阻碍了我们对大脑发育理解的进展。在此,我们展示了一个多模态三维发育通用坐标框架(DevCCF),它涵盖了小鼠胚胎期第(E)11.5天、E13.5天、E15.5天、E18.5天,以及出生后第(P)4天、P14天和P56天,并具有由发育本体定义的解剖学分割。在每个年龄段,DevCCF的特征包括通过磁共振成像创建的未变形的形态学平均图谱模板,以及与光片荧光显微镜的高分辨率模板进行配准的模板。每个年龄段由专家精心策划的三维解剖学分割遵循更新后的前脑模型,并且可以通过交互式三维网络可视化工具进行探索。作为一个应用案例,我们使用DevCCF揭示了胚胎大脑中γ-氨基丁酸能神经元的出现。此外,我们将艾伦通用坐标框架v3(Allen CCFv3)整合到具有立体定位坐标的P56模板中,并将空间转录组细胞类型数据与发育本体进行映射。总之,DevCCF是一个可公开获取的资源,可用于大规模数据整合,以全面了解大脑发育。