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Thread: New study focuses on neurons in spinal cord

  1. #1
    Member chris t4's Avatar
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    Nov 2003

    New study focuses on neurons in spinal cord


    "A research team at the University of Chicago has discovered a crucial signaling pathway that controls the growth of nascent nerves within the spinal cord,guiding them toward the brain during development.

    The study,published in the Dec, 12,2003,issue of the journal Science,solves a long-standing scientific mystery.It may also help restore function to people with paralyzing spinal cord injuries"

    If you have read this Dr.Young,could you elaborate on your thoughts about this new finding and if it will be a cure or a step closer to finding a cure? Also what are the nascent nerves?

  2. #2
    Hi KrisT4,

    Here are the original articles, there wasn't much discussion about it.

  3. #3
    kris, the article describes a paper, one of many that have been published in the past ten years, describing guidance molecules in the spinal cord. While the work is interesting, I was not impressed by the claim that this is "the first guidance mechanism that regulates regulates growth of nerve cells up and down the spinal cord". It is a very carefully worded sentence with subtle implications that would escape somebody who is not familiar with the large numbers of studies that have shown multiple guidance mechanisms and multiple regulators of nerve cell growth that are present in the spinal cord. The only reason that they were able to make such an exaggerated claim is that the study is from Mark Tessier-Lavigne's laboratory, the laboratory that discovered many other guidance mechanisms.

    Here is the abstract of the paper:
    • Lyuksyutova AI, Lu CC, Milanesio N, King LA, Guo N, Wang Y, Nathans J, Tessier-Lavigne M and Zou Y (2003). Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling. Science. 302: 1984-8. Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, IL 60637, USA. Commissural neurons in the mammalian dorsal spinal cord send axons ventrally toward the floor plate, where they cross the midline and turn anteriorly toward the brain; a gradient of chemoattractant(s) inside the spinal cord controls this turning. In rodents, several Wnt proteins stimulate the extension of commissural axons after midline crossing (postcrossing). We found that Wnt4 messenger RNA is expressed in a decreasing anterior-to-posterior gradient in the floor plate, and that a directed source of Wnt4 protein attracted postcrossing commissural axons. Commissural axons in mice lacking the Wnt receptor Frizzled3 displayed anterior-posterior guidance defects after midline crossing. Thus, Wnt-Frizzled signaling guides commissural axons along the anterior-posterior axis of the spinal cord.

    The authors found that the Wnt family of proteins may play a role in the dorsal-ventral guidance of commissural axons. The Wnt family of proteins was first discovered in over a decade ago to bind to a receptor called "frizzled" in drosophila (fruitfly), xenopus laevis (African clawed toad), and mammals. Wnt proteins have been implicated in the development of brain, limbs, and other organs. Animals that are missing Wnt-1, for example, do not develop their brains, showing clearly that Wnt proteins play an important role in development.

    Many other proteins bearing whimsical names such as "sonic hedgehog", "disheveled", "frodo", "slits", "netrin", "semaphorin", etc. have been shown to influence neuronal migration, differentiation, and axonal growth in the brain and spinal cord. In fact, over a decade ago, Tessier-Lavigne had discovered the diffusable protein called "netrin" which was the first factor know to attract axons to the mid-ventral floor of the brainstem, accounting for the crossing over of spinal tracts.

    This study showed that when they applied Wnt proteins to the spinal cord, it attracted axons. Furthermore, mice that are deficient in "frizzled3" receptors showed evidence of misdirected axonal growth. Since Wnt is known to bind to "frizzled3", they suggest that Wnt plays a role in attracting axons towards the brain. What they suggest is plausible but far from application to improve function regeneration in the spinal cord. It is not known whether Wnt proteins or their equivalents are expressed in injured spinal cords. There is some evidence to suggest that axonal growth, if started in spinal cord white matter and when axonal growth inhibitors such as Nogo and CSPG are neutralized, will continue long distances in the spinal cord. This may be with or without Wnt. It is not clear that Wnt is necessary or sufficient for guidance. The experiments showing grossly abnormal axonal growth in the absence of "frizzled3" receptors may be explained in several other ways.

    In short, this is a interesting paper but the connection to treatment of spinal cord injury is still quite distant right now. This is a paper to keep in our bonnets and someday it will be useful for understanding what guides axonal growth after injury.


    [This message was edited by Wise Young on 02-09-04 at 09:44 AM.]

  4. #4
    I just saw this article entitled "Fraud spurs Cell paper retraction" in the New Scientist today and realized that it was over the WNT gene that I talked about here.

    Summarizing briefly, a Columbia University researcher retracts a paper from the journal Cell last week due to fabricated data. The work was done in the laboratory of Gary Struhl of the Howard Hughes Medical Institute at Columbia. The paper was published in 2002 and challenged conventional thinking about Wnt signalling. The paper, based on work done by postodoctoral fellow Siu Kwong Chan, argued that a receptor for Wnt called Armadillo is tethered in the membrane and tranduced the signals without entering the nucleus of the cell. Struhl himself tried to replicate the experiment and found the opposite result. When Struhl confronted Chan with this, Chan indicated that some of the experiments had not been performed or showed different results. Other scientists also had not been able to replicate the results. Marian Bienz rom the Medical Research Council Laboraotry of Molecular Biology in Cambridge UK pointed that Struhl had an earlier retraction of a Nature paper in 1996 and commented "However, he then published an exoneration of that Nature paper, in Nature 1997, together with Chan! It's all the more remarkable since Struhl runs a small group, and has only published with 3 or 4 coauthors from his own lab in the last 7 years. How can this happen twice?" She also pointed out that review process failed and that one of the images was "used twice (though rotated and cropped differently the second time) for two different constructs!" This went unnoticed originally, but had later been corrected by Chan and Struhl.

    All this points to the importance of replication in science, that even work from respected laboratories should be taken with a grain of salt until the work has been replicated by another laboratory. This is a particularly poignant case because it involves a family of proteins that may play a role in spinal cord injury.


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