Transcriptional repression of the growth-associated T alpha1 alpha-tubulin gene by target contact.
In this report, we address the molecular mechanisms that regulate axonal growth by focusing on the gene for one of the major axonal cytoskeletal proteins, T alpha1 alpha-tubulin. During the developmental growth of sympathetic neurons, transcription of a beta-galactosidase transgene driven by the T alpha1 promoter (T alpha1:nlacZ) was high until the time of target innervation and neuronal maturation, when it decreased significantly. In mature animals, T alpha1:nlacZ transcription remained relatively low until target contact was experimentally disrupted; when facial motoneurons were axotomized, T alpha1:nlacZ transgene expression increased, was maximal for 1-7 days, and, if neurons regenerated and reinnervated their target musculature, returned to control levels by 49 days. In contrast, if regeneration and reestablishment of target contact were inhibited, transgene expression remained elevated. To determine whether this increased transcription was due to the loss of target contact or to axonal loss, we transected sympathetic neurons that project to the eye either close to or far from their cell bodies. In both cases, when target contact was severed, T alpha1:nlacZ transcription increased. These experiments indicate that transcription of the T alpha1 alpha-tubulin promoter is repressed by target contact in both developing and mature neurons. We suggest that this repression is due to a target-derived "stop-growth" factor that retrogradely signals to regulate transcription of this and other genes that are required for axonal growth.
Wu
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W
Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Canada.
Gloster
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Miller
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D000818:Animals; D001369:Axons / Q000502:physiology*; D002450:Cell Communication / Q000235:genetics*; D005154:Facial Nerve / Q000166:cytology / Q000502:physiology / Q000601:surgery; D005786:Gene Expression Regulation / Q000502:physiology; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000235:genetics; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000166:cytology / Q000601:surgery; D014158:Transcription, Genetic / Q000502:physiology*; D019076:Transgenes / Q000502:physiology; D014404:Tubulin / Q000235:genetics*
D014404:Tubulin