Axotomy-Induced Smad1 Activation Promotes Axonal Growth in Adult Sensory Neurons
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...
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| Veröffentlicht in: | The Journal of neuroscience 2009-06, Vol.29 (22), p.7116-7123 |
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| creator | Zou, Hongyan Ho, Carole Wong, Karen Tessier-Lavigne, Marc |
| description | 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 of Smad1 by axotomy is a key component of the transcriptional switch that promotes an enhanced growth state of adult sensory neurons. |
| doi_str_mv | 10.1523/JNEUROSCI.5397-08.2009 |
| format | Article |
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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. 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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 of Smad1 by axotomy is a key component of the transcriptional switch that promotes an enhanced growth state of adult sensory neurons.</description><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Axons - drug effects</subject><subject>Axons - physiology</subject><subject>Axotomy - methods</subject><subject>Bone Morphogenetic Protein 2 - pharmacology</subject><subject>Bone Morphogenetic Protein 4 - pharmacology</subject><subject>Brief Communications</subject><subject>Cells, Cultured</subject><subject>Enzyme Activation - drug effects</subject><subject>Functional Laterality</subject><subject>Ganglia, Spinal - cytology</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Mice</subject><subject>Microarray Analysis</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>Sensory Receptor Cells - cytology</subject><subject>Sensory Receptor Cells - drug effects</subject><subject>Sensory Receptor Cells - physiology</subject><subject>Smad1 Protein - genetics</subject><subject>Smad1 Protein - metabolism</subject><subject>Tubulin - metabolism</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkEtPAjEUhRujUUT_AunO1eDta4ZuTAhRxBAxouumdFoZMzM17cDIv3cIxsfqLs53zk0-hAYEhkRQdv3wePv6vFhOZkPBZJbAaEgB5BHqdalMKAdyjHpAM0hSnvEzdB7jOwBkQLJTdEYkl5ww3kNP40_f-GqXzOp8Y2yOl5XOCR6bptjqpvA1fgq-8o2NuCNrXeJp8G2zxkWNx_mmbPDS1tGHHX60m-DreIFOnC6jvfy-ffR6d_syuU_mi-lsMp4nRqSsSVIngDvLpAOeg3SUCkkAbCq4deAkS60hBkbcUMM1c1wYKk2eC55ZLleC9dHNYfdjs6psbmzdBF2qj1BUOuyU14X6n9TFWr35raIZkyBlN5AeBkzwMQbrfroE1N6x-nGs9o4VjNTecVcc_P38W_uW2gFXB2BdvK3bIlgVK12WHU5U27ZUKkpVRkjKvgApKYga</recordid><startdate>20090603</startdate><enddate>20090603</enddate><creator>Zou, Hongyan</creator><creator>Ho, Carole</creator><creator>Wong, Karen</creator><creator>Tessier-Lavigne, Marc</creator><general>Soc Neuroscience</general><general>Society for Neuroscience</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20090603</creationdate><title>Axotomy-Induced Smad1 Activation Promotes Axonal Growth in Adult Sensory Neurons</title><author>Zou, Hongyan ; Ho, Carole ; Wong, Karen ; Tessier-Lavigne, Marc</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c563t-6f504fe39f04d09f2259100e654ef0f936ec1c084c2c4a3f45c29cdd547e49b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Axons - drug effects</topic><topic>Axons - physiology</topic><topic>Axotomy - methods</topic><topic>Bone Morphogenetic Protein 2 - pharmacology</topic><topic>Bone Morphogenetic Protein 4 - pharmacology</topic><topic>Brief Communications</topic><topic>Cells, Cultured</topic><topic>Enzyme Activation - drug effects</topic><topic>Functional Laterality</topic><topic>Ganglia, Spinal - cytology</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Mice</topic><topic>Microarray Analysis</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>Sensory Receptor Cells - cytology</topic><topic>Sensory Receptor Cells - drug effects</topic><topic>Sensory Receptor Cells - physiology</topic><topic>Smad1 Protein - genetics</topic><topic>Smad1 Protein - metabolism</topic><topic>Tubulin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zou, Hongyan</creatorcontrib><creatorcontrib>Ho, Carole</creatorcontrib><creatorcontrib>Wong, Karen</creatorcontrib><creatorcontrib>Tessier-Lavigne, Marc</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zou, Hongyan</au><au>Ho, Carole</au><au>Wong, Karen</au><au>Tessier-Lavigne, Marc</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Axotomy-Induced Smad1 Activation Promotes Axonal Growth in Adult Sensory Neurons</atitle><jtitle>The Journal of neuroscience</jtitle><addtitle>J Neurosci</addtitle><date>2009-06-03</date><risdate>2009</risdate><volume>29</volume><issue>22</issue><spage>7116</spage><epage>7123</epage><pages>7116-7123</pages><issn>0270-6474</issn><eissn>1529-2401</eissn><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. 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| subjects | Analysis of Variance Animals Axons - drug effects Axons - physiology Axotomy - methods Bone Morphogenetic Protein 2 - pharmacology Bone Morphogenetic Protein 4 - pharmacology Brief Communications Cells, Cultured Enzyme Activation - drug effects Functional Laterality Ganglia, Spinal - cytology Gene Expression Profiling - methods Gene Expression Regulation - drug effects Mice Microarray Analysis RNA, Small Interfering - pharmacology Sensory Receptor Cells - cytology Sensory Receptor Cells - drug effects Sensory Receptor Cells - physiology Smad1 Protein - genetics Smad1 Protein - metabolism Tubulin - metabolism |
| title | Axotomy-Induced Smad1 Activation Promotes Axonal Growth in Adult Sensory Neurons |
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