Bota, M. | bioRxiv Science

bioRxiv2024

A three-dimensional histological cell atlas of the developing human brain

The human brain is believed to contain a full complement of neurons by the time of birth together with a substantial amount of the connectivity architecture, even though a significant amount of growth occurs postnatally. The developmental process leading to this outcome is not well understood in humans in comparison with model organisms. Previous magnetic resonance imaging (MRI) studies give three-dimensional coverage but not cellular resolution. In contrast, sparsely sampled histological or spatial omics analyses have provided cellular resolution but not dense whole brain coverage. To address the unmet need to provide a quantitative spatiotemporal map of developing human brain at cellular resolution, we leveraged tape-transfer assisted serial section histology to obtain contiguous histological series and unbiased imaging with dense coverage. Interleaved 20 thick Nissl and H&E series and MRI volumes are co-registered into multimodal reference volumes with 60 isotropic resolution, together with atlas annotations and a stereotactic coordinate system based on skull landmarks. The histological atlas volumes have significantly more contrast and texture than the MRI volumes. We computationally detect cells brain-wide to obtain quantitative characterization of the cytoarchitecture of the developing brain at 13-14 and 20-21 gestational weeks, providing the first comprehensive regional cell counts and characterizing the differential growth of the different brain compartments. Morphological characteristics permit segmentation of cell types from histology. We detected and quantified brain-wide distribution of mitotic figures representing dividing cells, providing an unprecedented spatiotemporal atlas of proliferative dynamics in the developing human brain. Further, we characterized the abundance and distribution of Cajal-Retzius cells, a transient cell population that plays essential roles in organizing glutamatergic cortical neurons into layers. Together, our study provides an unprecedented quantitative window into the developing human brain and the reference volumes and coordinate space should be useful for integrating spatial omics data sets with dense histological context.

neuroscience↗

bioRxiv2024

Establishing neuroanatomical correspondences across mouse and marmoset brain structures

Interest in the common marmoset is growing due to evolutionarily proximity to humans compared to laboratory mice, necessitating a comparison of mouse and marmoset brain architectures, including connectivity and cell type distributions. Creating an actionable comparative platform is challenging since these brains have distinct spatial organizations and expert neuroanatomists disagree. We propose a general theoretical framework to relate named atlas compartments across taxa and use it to establish a detailed correspondence between marmoset and mice brains. Contrary to conventional wisdom that brain structures may be easier to relate at higher levels of the atlas hierarchy, we find that finer parcellations at the leaf levels offer greater reconcilability despite naming discrepancies. Utilizing existing atlases and associated literature, we created a list of leaf-level structures for both species and establish five types of correspondence between them. One-to-one relations were found between 43% of the structures in mouse and 47% in marmoset, whereas 25% of mouse and 10% of marmoset structures were not relatable. The remaining structures show a set of more complex mappings which we quantify. Implementing this correspondence with volumetric atlases of the two species, we make available a computational tool for querying and visualizing relationships between the corresponding brains. Our findings provide a foundation for computational comparative analyses of mesoscale connectivity and cell type distributions in the laboratory mouse and the common marmoset.

neuroscience↗