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Thread: Gene linked several ways to Idiopathic Scoliosis - flow defect in cerebrospinal fluid

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  1. #1
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    Gene linked several ways to Idiopathic Scoliosis - flow defect in cerebrospinal fluid

    Seems pretty tight... we will see what happens.

    http://esciencenews.com/sources/scie...spine.curvatur

    [Report] Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature

    Thursday, June 9, 2016 - 14:42 in Health & Medicine
    Idiopathic scoliosis (IS) affects 3% of children worldwide, yet the mechanisms underlying this spinal deformity remain unknown. Here we show that ptk7 mutant zebrafish, a faithful developmental model of IS, exhibit defects in ependymal cell cilia development and cerebrospinal fluid (CSF) flow. Transgenic reintroduction of Ptk7 in motile ciliated lineages prevents scoliosis in ptk7 mutants, and mutation of multiple independent cilia motility genes yields IS phenotypes. We define a finite developmental window for motile cilia in zebrafish spine morphogenesis. Notably, restoration of cilia motility after the onset of scoliosis blocks spinal curve progression. Together, our results indicate a critical role for cilia-driven CSF flow in spine development, implicate irregularities in CSF flow as an underlying biological cause of IS, and suggest that noninvasive therapeutic intervention may prevent severe scoliosis. Authors: D. T. Grimes, C. W. Boswell, N. F. C. Morante, R. M. Henkelman, R. D. Burdine, B. Ciruna
    Last edited by Pooka1; 06-11-2016 at 07:36 PM.
    Sharon, mother of identical twin girls with scoliosis

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    Is this the reason why Chiari is linked with scoliosis?

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    Good question
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

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    Here is a more detailed discussion. I agree with the one researcher who said this series of experiments was elegant. I don't use that word lightly and I assume other scientists don't either. The more I read the tighter the case seems. But we have to wait and see... science is a tough game.

    https://www.sciencedaily.com/release...0610140806.htm

    Some excerpts...

    Hazel Sive, a professor in biology at the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology who was not involved in the study, is an expert in the use of zebrafish to study vertebrate development.

    "This study is an important step forward in understanding events underlying spinal curvature," Sive said. "In an elegant set of experiments, the authors take advantage of the outstanding zebrafish system to define that cilia function and perhaps cerebrospinal fluid flow is required for normal spinal cord development."
    There are other genes that control cilia motility that were manipulated to produce scoliosis in the zebrafish. Maybe this multiplicity of genes is what has thwarted attempts to determine inheritance patterns. IS is known to be genetic but the pattern has been elusive.

    The researchers also tested other motile-cilia gene mutations to see whether they disrupt cerebrospinal fluid flow and cause spine curvature. Daniel Grimes, a postdoctoral research associate, and Nicholas Morante, a graduate student, both in the Burdine lab in Princeton's Department of Molecular Biology, studied four such mutations in genes called ccdc40, ccdc151, dyx1c1 and c21orf59. They found that all four gene mutations led to curvature of the spine in zebrafish.
    And this hopeful note...

    Several additional lines of evidence point to links between motile cilia dysfunction, cerebrospinal fluid flow disruption and idiopathic scoliosis, Burdine said. For example, individuals with primary ciliary dyskinesia, a rare genetic disorder that causes defects in the movement of cilia lining the respiratory tract, have an elevated risk for scoliosis. Also, scoliosis is prevalent in humans with conditions such as tumors that obstruct cerebrospinal fluid flow.

    The next step will be to understand the mechanisms by which disrupted cerebrospinal fluid flow causes the spine to curve, Burdine said.

    "Now that we can study idiopathic scoliosis in zebrafish," she said, "we can begin to identify molecular pathways that are involved in spine curvature, and hopefully, find therapeutic targets to address this condition."
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

  5. #5
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    Quote Originally Posted by flerc View Post
    Is this the reason why Chiari is linked with scoliosis?
    As far as the research I've done, and it's posted somewhere on here Chiari Malformations are associated with left primary curves, affecting 40% of those with convect left curves. I'm not going to go digging for it again. I posted the study already.
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    Quote Originally Posted by rohrer01 View Post
    As far as the research I've done, and it's posted somewhere on here Chiari Malformations are associated with left primary curves, affecting 40% of those with convect left curves. I'm not going to go digging for it again. I posted the study already.
    I Just scanned some abstracts which are have similar findings... apparently the curve direction is highly correlated with side of most herniated tonsil and most displaced syrinx. For example...

    http://www.ncbi.nlm.nih.gov/pubmed/22744510

    The thoracic scoliosis in these patients was usually convex not only to the dominant side of asymmetrically displaced tonsils, but also to the side of eccentrically located syrinx, indicating that the asymmetry of tonsillar displacement and syrinx location might be involved in the regulation of curve direction.
    Because of this, many of these authors argue that this type of scoliosis is not idiopathic. All of this seems consistent with the genetic work pointing to the CSF flow defect. The puzzle pieces are coming together.
    Last edited by Pooka1; 06-18-2016 at 11:41 AM.
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

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