Biology subjects

Lütje, L.

Publications and source records attributed to Lütje, L..

3 recordsLinked to original sources

bioRxiv2025

Perfect imperfections: seeking molecular and cellular asymmetries in the mouse brain

Although perfect symmetry is a mathematical ideal, many Bilateria exhibit left-right asymmetries of body, brain and behavior that are adaptive 1-3. In the human brain, various aspects of cognition are lateralized, including language 4 and handedness 5, which rely on left hemisphere dominance in most people. Brain hemispheric specialization can support parallel processing, neural efficiency, and action selection 3,6, while atypical structural or functional asymmetries are often found in neuropsychiatric disorders 7-10. Mice may be useful models for studying brain asymmetry because they show hemispheric differences of structure 11,12 and neurophysiology 13, but the extent to which molecular and cellular differences are involved remains unknown. We applied spatial transcriptomics with single molecule resolution to coronal sections from 31 adult mouse brains, to assess left-right differences of gene expression and cell types. Sections were chosen to capture the hippocampus and auditory cortex, as these two regions have shown the most prior evidence for functional asymmetry 13-15. In the hippocampus, Crhr1 (Corticotropin-Releasing Hormone Receptor 1) was more highly expressed in the pyramidal layers of CA1, CA3 and the dentate gyrus of the left hemisphere compared to the right. In the auditory cortex, three principal components capturing transcriptomic variation showed hemispheric differences, including prominent contributions from genes that have shown associations with human brain asymmetry. Overall cellular density and cell type proportions generally showed no significant hemispheric differences, with Car3 cortical excitatory neurons showing the most laterality. The transcriptional left-right differences that we found may relate to functional asymmetries for learning, memory and hearing. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=195 SRC="FIGDIR/small/675542v1_ufig1.gif" ALT="Figure 1"> View larger version (119K): org.highwire.dtl.DTLVardef@1530502org.highwire.dtl.DTLVardef@16dd244org.highwire.dtl.DTLVardef@107950corg.highwire.dtl.DTLVardef@ca52a3_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIMolecular and cellular basis of functional brain asymmetry is barely known C_LIO_LISpatial transcriptomics with cellular resolution applied to mouse brain coronal sections C_LIO_LIGenes implicated in human brain asymmetry showed hemispheric differences in mice C_LIO_LINo hemispheric differences of cell type abundances C_LI

neuroscience↗

bioRxiv2024

The chromatin remodeler CHD3 is highly expressed in mature neurons and regulates genes involved in synaptic development and function

Changes in the dynamics of chromatin state that control spatiotemporal gene expression patterns are crucial during brain development. CHD3 is a chromatin remodeler that is highly expressed during neurogenesis and that functions as a core member of the NuRD complex, a large multiprotein complex mediating chromatin state. Genetic disruptions in CHD3 have been implicated in a neurodevelopmental disorder characterized by intellectual disability, macrocephaly and severe speech deficits. To study the roles of CHD3 during early human brain development, we generated induced pluripotent stem cells with heterozygous and homozygous loss-of-function mutations, differentiated them into unguided neural organoids and cortical neurons, and analyzed these by immunohistochemistry, bulk RNA-, single-cell RNA-, and ChIP-sequencing. Loss of CHD3 expression had no detectable effects on early neuroepithelium formation and organoid growth, nor did it significantly affect cell type composition or neuronal differentiation speed. Instead, upon loss of CHD3, we observed dysregulation of genes related to axon guidance and synapse development across all datasets, identifying a novel role for the protein as a regulator that facilitates neurogenesis, in particular neuronal maturation. Our results based on genetically engineered knockout organoids pave the way for future studies modeling the neurobiological pathways affected in CHD3-related disorder.

neuroscience↗

bioRxiv2023

FriendlyClearMap: An optimized toolkit for mouse brain mapping and analysis

Tissue clearing is currently revolutionizing neuroanatomy by enabling organ-level imaging with cellular resolution. However, currently available tools for data analysis require a significant time investment for training and adaptation to each laboratorys use case, which limits productivity. Here, we present FriendlyClearMap, an integrated toolset that makes ClearMap1 and ClearMap2s CellMap pipeline easier to use, extends its functions, and provides Docker Images from which it can be run with minimal time investment. We also provide detailed tutorials for each step of the pipeline. For more precise alignment, we add a landmark-based atlas registration to ClearMaps functions as well as include young mouse reference atlases for developmental studies. We provide alternative cell segmentation method besides ClearMaps threshold-based approach: Ilastiks Pixel Classification, importing segmentations from commercial image analysis packages and even manual annotations. Finally, we integrate BrainRender, a recently released visualization tool for advanced 3D visualization of the annotated cells. As a proof-of-principle, we use FriendlyClearMap to quantify the distribution of the three main GABAergic interneuron subclasses (Parvalbumin+, Somatostatin+, and VIP+) in the mouse fore- and midbrain. For PV+ neurons, we provide an additional dataset with adolescent vs. adult PV+ neuron density, showcasing the use for developmental studies. When combined with the analysis pipeline outlined above, our toolkit improves on the state-of-the-art packages by extending their function and making them easier to deploy at scale.

neuroscience↗