title: Testing the role of the cell-surface molecule Thy-1 in regeneration and plasticity of connectivity in the CNS.
abstract: Thy-1 is a cell-surface signaling molecule of the Ig superfamily implicated in the regulation of neurite outgrowth, synaptic function and plasticity. There is, however, no consensus as to its precise function in the nervous system, and it remains unclear or untested as to what its role is in the development, maintenance and plasticity of neuronal connectivity in the intact brain and whether it is essential for any of the purported functions which have been attributed to it based largely on in vitro bioassays. Here, we have engineered transgenic mice with a targeted deletion of the Thy-1 gene and, after characterizing the development of their corticospinal and thalamocortical pathways, subjected them at adulthood to paradigms of axonal regeneration and plasticity which can be readily induced during development. Quantitative analyses of the brains and spinal cords of adult null mutants showed normal cellular organization, normal anatomical features of the corticospinal and thalamocortical pathways, and basic neurophysiological properties of thalamocortical synaptic transmission which were quantitatively indistinguishable from wild-type mice. Despite the absence of Thy-1, corticospinal axons in adult mutants failed to exhibit overt regeneration following spinal cord lesion; likewise, the terminal arbors of ventrobasal thalamocortical axons also failed to reorganize in adult barrel cortex in response to whisker cautery, although they did so during a developmental critical period identical to that displayed by wild-type mice.Taken together, these results suggest that Thy-1 is not essential for the normal development and maintenance of major axon pathways and functional synaptic connections, nor would it appear to be critically important for inhibiting or promoting axonal growth, regeneration and plasticity in the developing and mature CNS.
authors.affiliation: Fishberg Research Center for Neurobiology and Program in Cell Adhesion, Box 1065, The Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029-6574, USA.
authors.forename: J Z
authors.initials: JZ
authors.lastname: Barlow
authors.forename: K A
authors.initials: KA
authors.lastname: Kelley
authors.forename: O
authors.initials: O
authors.lastname: Bozdagi
authors.forename: G W
authors.initials: GW
authors.lastname: Huntley
mesh_terms: D000344:Afferent Pathways / Q000254:growth & development; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D001369:Axons / Q000378:metabolism; D015152:Blotting, Northern; D015139:Blotting, Southern; D018929:Cell Culture Techniques; D002490:Central Nervous System / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D004594:Electrophysiology; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009416:Nerve Regeneration; D009473:Neuronal Plasticity; D011712:Pyramidal Tracts / Q000254:growth & development / Q000293:injuries; D012683:Sensory Deprivation; D013003:Somatosensory Cortex / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000276:immunology / Q000503:physiopathology; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism*; D014738:Vibrissae
chemical_list: D000954:Antigens, Surface; D018800:Thy-1 Antigens