Author:
Xu Huixin,Dugué Guillaume P.,Cantaut-Belarif Yasmine,Lejeune François-Xavier,Gupta Suhasini,Wyart Claire,Lehtinen Maria K.
Abstract
AbstractReissner’s fiber (RF) is an extracellular polymer comprising the large monomeric protein SCO-spondin (SSPO) secreted by the subcommissural organ (SCO) that extends through cerebrospinal fluid (CSF)-filled ventricles into the central canal of the spinal cord. In zebrafish, RF and CSF-contacting neurons (CSF-cNs) form an axial sensory system that detects spinal curvature, instructs morphogenesis of the body axis, and enables proper alignment of the spine. In mammalian models, RF has been implicated in CSF circulation. However, challenges in manipulating Sspo, an exceptionally large gene of 15,719 nucleotides, with traditional approaches has limited progress. Here, we generated a Sspo knockout mouse model using CRISPR/Cas9-mediated genome-editing. Sspo knockout mice lacked RF-positive material in the SCO and fibrillar condensates in the brain ventricles. Remarkably, Sspo knockout brain ventricle sizes were reduced compared to littermate controls. Minor defects in thoracic spine curvature were detected in Sspo knockouts, which did not alter basic motor behaviors tested. Altogether, our work in mouse demonstrates that SSPO and RF regulate ventricle size during development but only moderately impact spine geometry.
Funder
William Randolph Hearst Fund
a Cotrel Spinal Research Foundation
Human Frontier Science Program (HFSP) research program grant
the New York Stem Cell Foundation
the European Research Council
National Institutes of Health
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Developmental Neuroscience,Neurology,General Medicine
Cited by
2 articles.
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