Axotomy-induced smad1 activation promotes axonal growth in adult sensory neurons

Hongyan Zou, Carole Ho, Karen Wong, Marc Tessier-Lavigne

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

Mature neurons have diminished intrinsic regenerative capacity. Axotomy of the peripheral branch of adult dorsal root ganglia (a "conditioning" lesion) triggers a transcription-dependent axon growth program. Here, we show that this growth program requires the function of the transcription factor Smad1. After peripheral axotomy, neuronal Smad1 is upregulated, and phosphorylated Smad1 accumulates in the nucleus. Both events precede the onset of axonal extension. Reducing Smad1 by RNA interference in vitro impairs axonal growth, and the continued presence of Smad1 is required to maintain the growth program. Furthermore, intraganglionic injection of BMP2 or 4, which activates Smad1, markedly enhances axonal growth capacity, mimicking the effect of a conditioning lesion. Thus, activation ofSmad1by axotomy is a key component of the transcriptional switch that promotes an enhanced growth state of adult sensory neurons.

Original languageEnglish
Pages (from-to)7116-7123
Number of pages8
JournalJournal of Neuroscience
Volume29
Issue number22
DOIs
StatePublished - 3 Jun 2009
Externally publishedYes

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