Role of Thy-1 Glycoprotein in Neurite Outgrowth

Jani, Harsha (1998). Role of Thy-1 Glycoprotein in Neurite Outgrowth. MPhil thesis The Open University.



In the peripheral nervous system (PNS), neurons regenerate axons following injury and reinnervate their target tissue. The substrate along which these axons extend is of critical importance. Mammalian central nervous system (CNS) neurons, normally unable to regenerate, can do so if given a permissive substrate. Adult axons will regenerate on embryonic CNS tissue and embryonic axons can grow in adult CNS environment but generally adult axons do not regenerate on adult glia. There are inhibitory molecules in the mature CNS environment that regulate growth. In this study I have examined the mature astrocyte-adult axon paradigm.

Thy-1, a glycoprotein consisting of 110 amino acids is present on mature axons. When transfected into neuroblastoma cell line NG1 15/401L, it inhibits neurite outgrowth on a monolayer of mature astrocytes. I have used primary sensory neurons derived from Thy-1 knockout mice to study the inhibitory effect of Thy-1. I have modified the original method for dissociating dorsal root ganglion cells from adult mice resulting in a population of DRG neurons that grow on average six times longer at 24 hours than other reported measurements. Using an image analysis system for measuring total neurite outgrowth, I have shown that Thy-1 does not prevent but significantly restricts neurite outgrowth over astrocytes. Preliminary experiments on embryonic DRG cells suggests that at a stage in development when Thy-1 is not present on neurons there is no difference in neurite outgrowth between Thy-1 positive and Thy-1 negative DRG cells. A growth restrictive role for Thy-1 is thus indicated. To fully understand the role of the axon-astrocyte interplay I have developed a three-dimensional in vitro system to study the extent to which Thy-1 is involved in this system.

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