TY - JOUR
T1 - The Reissner Fiber Is Highly Dynamic In Vivo and Controls Morphogenesis of the Spine
AU - Troutwine, Benjamin R.
AU - Gontarz, Paul
AU - Konjikusic, Mia J.
AU - Minowa, Ryoko
AU - Monstad-Rios, Adrian
AU - Sepich, Diane S.
AU - Kwon, Ronald Y.
AU - Solnica-Krezel, Lilianna
AU - Gray, Ryan S.
N1 - Funding Information:
We thank Esteban Rodriguez and Maria Montserrat Guerra (Universidad Austral de Chile) for their generous gift of the AFRU antiserum. We thank Chole Rose and Brian Ciruna for generously sharing the scospondinhsc105 mutant zebrafish prior to publication. We thank Sierra Szkrybalo and Melisa N. Bayrak for assistance with zebrafish experiments. We thank Drs. John Wallingford and Claire Wyart for critical comments on this manuscript. We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The center is partially supported by NCI Cancer Center Support Grant no. P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA grant no. UL1TR002345 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. Research reported in this publication was supported in part by a grant from Spinal Cord Injury/Disease Research Program (SCIDRP) (to L.S.-K. and Steve Johnson), the Scoliosis Research Society (SRS), the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH under award number AR072009 to (R.S.G.) and AR066061 to (R.Y.K.), and by the National Institute of Child Health and Human Development of the NIH under award number P01HD084387 (L.S.-K.). R.S.G. D.S.S. and L.S.-K. set up the forward genetic screen and isolated the scospondin mutant alleles; P.G. and R.S.G. performed WGS/WES and mapping of the mutants; A.M.-R. and R.Y.K. performed microCT imaging and analysis; B.R.T. and M.J.K. performed immunohistochemistry, confocal imaging, and statistical analysis; B.R.T. engineered the scospondin-GFP knockin, with help with screening and genotyping by R.M.; and R.S.G. and L.S.-K. funded and supervised the project. R.S.G. conceived the project and wrote the article with input from B.R.T. R.Y.K. D.S.S. and L.S.-K. The authors declare no competing interests.
Funding Information:
We thank Esteban Rodriguez and Maria Montserrat Guerra (Universidad Austral de Chile) for their generous gift of the AFRU antiserum. We thank Chole Rose and Brian Ciruna for generously sharing the scospondin hsc105 mutant zebrafish prior to publication. We thank Sierra Szkrybalo and Melisa N. Bayrak for assistance with zebrafish experiments. We thank Drs. John Wallingford and Claire Wyart for critical comments on this manuscript. We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The center is partially supported by NCI Cancer Center Support Grant no. P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA grant no. UL1TR002345 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research . This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. Research reported in this publication was supported in part by a grant from Spinal Cord Injury/Disease Research Program (SCIDRP) (to L.S.-K. and Steve Johnson), the Scoliosis Research Society (SRS), the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH under award number AR072009 to (R.S.G.) and AR066061 to (R.Y.K.), and by the National Institute of Child Health and Human Development of the NIH under award number P01HD084387 (L.S.-K.).
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/6/22
Y1 - 2020/6/22
N2 - Cerebrospinal fluid (CSF) physiology is important for the development and homeostasis of the central nervous system, and its disruption has been linked to scoliosis in zebrafish [1, 2]. Suspended in the CSF is an extracellular structure called the Reissner fiber, which extends from the brain through the central canal of the spinal cord. Zebrafish scospondin-null mutants are unable to assemble a Reissner fiber and fail to form a straight body axis during embryonic development [3]. Here, we describe hypomorphic missense mutations of scospondin, which allow Reissner fiber assembly and extension of a straight axis. However, during larval development, these mutants display progressive Reissner fiber disassembly, which is concomitant with the emergence of axial curvatures and scoliosis in adult animals. Using a scospondin-GFP knockin zebrafish line, we demonstrate several dynamic properties of the Reissner fiber in vivo, including embryonic fiber assembly, the continuous rostral to caudal movement of the fiber within the brain and central canal, and subcommissural organ (SCO)-spondin-GFP protein secretion from the floor plate to merge with the fiber. Finally, we show that disassembly of the Reissner fiber is also associated with the progression of axial curvatures in distinct scoliosis mutant zebrafish models. Together, these data demonstrate a critical role for the Reissner fiber for the maintenance of a straight body axis and spine morphogenesis in adult zebrafish. Our study establishes a framework for future investigations to address the cellular effectors responsible for Reissner-fiber-dependent regulation of axial morphology. Video Abstract: [Figure presented] Troutwine et al. report a new scospondin-GFP knockin zebrafish strain and demonstrate intriguing dynamic properties of the Reissner fiber in the brain and central canal in vivo. Using forward genetics and cell biological approaches, they demonstrate that Reissner fiber assembly is critical during spine morphogenesis in zebrafish.
AB - Cerebrospinal fluid (CSF) physiology is important for the development and homeostasis of the central nervous system, and its disruption has been linked to scoliosis in zebrafish [1, 2]. Suspended in the CSF is an extracellular structure called the Reissner fiber, which extends from the brain through the central canal of the spinal cord. Zebrafish scospondin-null mutants are unable to assemble a Reissner fiber and fail to form a straight body axis during embryonic development [3]. Here, we describe hypomorphic missense mutations of scospondin, which allow Reissner fiber assembly and extension of a straight axis. However, during larval development, these mutants display progressive Reissner fiber disassembly, which is concomitant with the emergence of axial curvatures and scoliosis in adult animals. Using a scospondin-GFP knockin zebrafish line, we demonstrate several dynamic properties of the Reissner fiber in vivo, including embryonic fiber assembly, the continuous rostral to caudal movement of the fiber within the brain and central canal, and subcommissural organ (SCO)-spondin-GFP protein secretion from the floor plate to merge with the fiber. Finally, we show that disassembly of the Reissner fiber is also associated with the progression of axial curvatures in distinct scoliosis mutant zebrafish models. Together, these data demonstrate a critical role for the Reissner fiber for the maintenance of a straight body axis and spine morphogenesis in adult zebrafish. Our study establishes a framework for future investigations to address the cellular effectors responsible for Reissner-fiber-dependent regulation of axial morphology. Video Abstract: [Figure presented] Troutwine et al. report a new scospondin-GFP knockin zebrafish strain and demonstrate intriguing dynamic properties of the Reissner fiber in the brain and central canal in vivo. Using forward genetics and cell biological approaches, they demonstrate that Reissner fiber assembly is critical during spine morphogenesis in zebrafish.
KW - Reissner fiber
KW - SCO-spondin
KW - scoliosis
KW - zebrafish
UR - http://www.scopus.com/inward/record.url?scp=85084992507&partnerID=8YFLogxK
U2 - 10.1016/j.cub.2020.04.015
DO - 10.1016/j.cub.2020.04.015
M3 - Article
C2 - 32386529
AN - SCOPUS:85084992507
VL - 30
SP - 2353-2362.e3
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 12
ER -