<div class="csl-bib-body">
<div class="csl-entry">Pende, M., Cregg, J. M., Saghafi, S., Broadbent, S., Avdibasic, A., Roeles, J., Papadopoulos, S.-C., Seaman, R. P., Pende, N., Solano Mateos, M., Katelyn Jamwal, Wunch, M., Pasierbek, P., Moreno-Cencerrado, A., Korchynska, S., Hauer, R., Anderson, P., Supper, P., Kastriti, M. E., … Murawala, P. (2026). <i>A uniform tissue-clearing framework and mesoSPIM-ultra enable cm-scale single-neuron tracing</i>. bioRxiv. https://doi.org/10.34726/12506</div>
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dc.identifier.uri
http://hdl.handle.net/20.500.12708/230143
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dc.identifier.uri
https://doi.org/10.34726/12506
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dc.description.abstract
Tissue-clearing and light-sheet microscopy have transformed volumetric imaging of intact organs, yet limited mechanistic understanding of dehydration-based clearing continues to constrain rational protocol design and broader applicability. Here, we define the cardinal chemical and physical principles underlying dehydration-based tissue-clearing and establish a new pipeline for large-volume imaging. To maximize imaging performance, we developed the “mesoSPIM-ultra”, an upgraded mesoSPIM platform with a temperature-controlled sample chamber, a large field-of-view (FoV) camera and specialized optics to achieve long-working-distance, high-resolution imaging of cleared samples. We applied this approach to investigate the projectome of Chx10+ neurons, a cell population with complex axonal morphologies along the entire mouse spinal-cord and brain, and implicated in ipsilateral orienting behaviors. By combining behavioral analysis with post-hoc single-neuron reconstructions, we revealed previously inaccessible branching architectures and long-range projections extending from the brainstem to the spinal cord. Together, our work establishes a mechanistic foundation for tissue-clearing and scalable imaging.