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SCO-spondin knockout mice exhibit small brain ventricles and mild spine deformation.

ABSTRACT: Reissner'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.

SUBMITTER: Xu H

PROVIDER: S-EPMC10696872 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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SCO-spondin knockout mice exhibit small brain ventricles and mild spine deformation.

Xu Huixin H Dugué Guillaume P GP Cantaut-Belarif Yasmine Y Lejeune François-Xavier FX Gupta Suhasini S Wyart Claire C Lehtinen Maria K MK

Fluids and barriers of the CNS 20231205 1

Reissner'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 implicate ...[more]

PMID: 38049798

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Project description:Cerebrospinal fluid is a clear fluid that occupies the ventricular and subarachnoid spaces within and around the brain and spinal cord. Cerebrospinal fluid is a dynamic signaling milieu that transports nutrients, waste materials and neuroactive substances that are crucial for the development, homeostasis and functionality of the central nervous system. The mechanisms that enable cerebrospinal fluid to simultaneously exert these homeostatic/dynamic functions are not fully understood. SCO-spondin is a large glycoprotein secreted since the early stages of development into the cerebrospinal fluid. Its domain architecture resembles a combination of a matricellular protein and the ligand-binding region of LDL receptor family. The matricellular proteins are a group of extracellular proteins with the capacity to interact with different molecules, such as growth factors, cytokines and cellular receptors; enabling the integration of information to modulate various physiological and pathological processes. In the same way, the LDL receptor family interacts with many ligands, including β-amyloid peptide and different growth factors. The domains similarity suggests that SCO-spondin is a matricellular protein enabled to bind, modulate, and transport different cerebrospinal fluid molecules. SCO-spondin can be found soluble or polymerized into a dynamic threadlike structure called the Reissner fiber, which extends from the diencephalon to the caudal tip of the spinal cord. Reissner fiber continuously moves caudally as new SCO-spondin molecules are added at the cephalic end and are disaggregated at the caudal end. This movement, like a conveyor belt, allows the transport of the bound molecules, thereby increasing their lifespan and action radius. The binding of SCO-spondin to some relevant molecules has already been reported; however, in this review we suggest more than 30 possible binding partners, including peptide β-amyloid and several growth factors. This new perspective characterizes SCO-spondin as a regulator of cerebrospinal fluid activity, explaining its high evolutionary conservation, its apparent multifunctionality, and the lethality or severe malformations, such as hydrocephalus and curved body axis, of knockout embryos. Understanding the regulation and identifying binding partners of SCO-spondin are crucial for better comprehension of cerebrospinal fluid physiology.

Dataset Information

SCO-spondin knockout mice exhibit small brain ventricles and mild spine deformation.

Publications

SCO-spondin knockout mice exhibit small brain ventricles and mild spine deformation.

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