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A role of netrin-1 in the dorsal spinal cord formation
https://ir.soken.ac.jp/records/1173
https://ir.soken.ac.jp/records/117375d07054-9a87-45a0-9534-731c75275c6e
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
要旨・審査要旨 (249.8 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2010-02-22 | |||||
| タイトル | ||||||
| タイトル | A role of netrin-1 in the dorsal spinal cord formation | |||||
| タイトル | ||||||
| タイトル | A role of netrin-1 in the dorsal spinal cord formation | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_46ec | |||||
| 資源タイプ | thesis | |||||
| 著者名 |
渡辺, 啓介
× 渡辺, 啓介 |
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| フリガナ |
ワタナベ, ケイスケ
× ワタナベ, ケイスケ |
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| 著者 |
WATANABE, Keisuke
× WATANABE, Keisuke |
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| 学位授与機関 | ||||||
| 学位授与機関名 | 総合研究大学院大学 | |||||
| 学位名 | ||||||
| 学位名 | 博士（理学） | |||||
| 学位記番号 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 総研大甲第971号 | |||||
| 研究科 | ||||||
| 値 | 生命科学研究科 | |||||
| 専攻 | ||||||
| 値 | 20 生理科学専攻 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2006-03-24 | |||||
| 学位授与年度 | ||||||
| 値 | 2005 | |||||
| 要旨 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Dorsal root ganglion (DRG) neurons extend axons to the specific targets in the gray matter of the spinal cord and convey somatic and visceral sensory information from peripheral tissues to the spinal cord. The projections of sensory axons to specific targets are crucial for the accurate perception of and reflex to external sensory information. During development, process of the axonal projections of DRG neurons is tightly regulated. During early embryogenesis, DRG axons enter the spinal cord at the dorsal root entry zone (DREZ) and then grow to the marginal zone longitudinally to form the dorsal funiculus without penetrating the dorsal gray matter. After a few days, proprioceptive afferents, which are involved in the muscle stretch reflex, penetrae the mantle layer and project ventrally through the dorsal layers. Subsequently, thermoceptive and nociceptive cutaneous sensory afferents start to send collaterals into the dorsal mantle layer and terminate in the dorsal-most laminae of the cord. Therefore, projection pattern of DRG axons show delay between formation of the dorsal funiculus in the marginal zone and extension of collaterals into the dorsal mantle layer, called the "waiting period". Based on this growth pattern of DRG axons, it has been presumed that repellant(s) and/or inhibitory cues transiently prevent sensory afferents from penetrating the dorsal spinal cord during the waiting period. In other words, the inhibitory cues are apparently required for correct patterning of sensory afferents. However, a diffusible guidance molecule(s) involved in sensory axon patterning in the dorsal spinal cord is totally unknown. <br/> Diffusible signals acting at distance, including the netrin, semaphorin and slit families, are important cues for the early guidance of neuronal pathways during development. Netrin-1,from the Sanskrit term "one who guides", is originally identified in the ventral midline of the neural tube as a axon guidance molecule during early embryogenesis; it is a long-range diffusible factor that exerts chemoattractive or chemorepulsive effects for distinct developing neural cells, thus regulating axon outgrowth and cell migration. The attractive effects of netrin appear to be mediated by a netrin receptor, Dcc, whereas Unc5 family receptorsare involved in mediating repulsive actions. Netrin secreted from cells in the floor plate directs many axons to midline. Netrin-1 is also weakly expressed in the developing dorsal spinal cord. However, roles of this dorsally derived netrin-1 remain totally unknown. Here he shows that dorsally derived netrin-1 controls the correct guidance of primary sensory axons. During the waiting period for primary sensory axons, netrin1 is transiently expressed or upregulated in the dorsal spinal cord, and the absence of <i>netrin-1</i> results in aberrant and premature projections of sensory axons, including both cutaneous and proprioceptive afferents, into the dorsal mantle layer without initial growth along the marzinal zone of the dorsal spinal cord. Thus, <i>netrin-1</i> deficient mice show loss of the waiting period･ He also demonstrates that aberrant projections of DRG axons is not due to the abnormal cell migration or patterning in the dorsal spinal cord, which is reported in the spinal cord development of <i>Dcc</i>knockout mice. To examine netrin-1 function on DRG axons, he has applied collagen gel culture experiment. Netrin-1 suppresses axon outgrowth from DRG explants in vitro. However, there did not seem to be a specific effect of netrin-1 on either axon attraction or repulsion. Netrin-1 expressed in the floor plate apparently influences the dorsal spinal cord in early stages. To examine dorsally derived netrin-1 is important for correct projections of DRG axons, he used <i>Gli2</i> mutant mice, which is devoid of the floor plate, and demonstrated that the mutant embryos show normal projections of the DRG axons.<br />Therefore, netrin-1 derived from the dorsal spinal cord, but not the floor plate, is involved in the correct projections of DRG axons. Furthemore, to elucidate on which netrin receptors the projections of sensory afferents are dependent, he analyzed the trajectories of sensory axons in netrin receptor <i>Dcc</i> mutant and <I>Unc5c<sup>rcm</sup></i>mutant mice. <I>Unc5c<sup>rcm</sup></i> mutant shows abnormal invasion of DRG axons as observed in <i>netrin-1</i>mutants, whereas the dorsal funiculus of <i>Dcc</i> mutant mice is normally established at early stage. These results clearly demonstrate that netrin-1 in the dorsal spinal cord acts as an inhibitory cue for primary sensory axons and thus serves as a critical signal for proper formation of sensory neural networks. | |||||
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| 値 | 有 | |||||
