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Dosage-dependent hedgehog signals integrated with Wnt/β-catenin signaling regulate external genitalia formation as an appendicular program
http://hdl.handle.net/2298/14871
http://hdl.handle.net/2298/14871c935d1cc-28b2-4631-b2e5-f368a2a3cf1b
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
3969.pdf (1.7 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2010-06-02 | |||||
| タイトル | ||||||
| タイトル | Dosage-dependent hedgehog signals integrated with Wnt/β-catenin signaling regulate external genitalia formation as an appendicular program | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題 | External genitalia, Genetic cascade, Hedgehog, Fgf, β-catenin (Ctnnb1), Cloaca, Appendages, Mouse | |||||
| 資源タイプ | ||||||
| 資源タイプ | journal article | |||||
| 著者 |
Miyagawa, Shinichi
× Miyagawa, Shinichi× Moon, Anne× Haraguchi, Ryuma× Inoue, Chie× Harada, Masayo× Nakahara, Chiaki× 鈴木, 堅太郎× Matsumaru, Daisuke× Kaneko, Takehito× Matsuo, Isao× Lei, Yang× Makoto, M. Taketo× Iguchi, Taisen× Evans, Sylvia M.× 山田, 源 |
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| 別言語の著者 |
山田, 源
× 山田, 源× 原口, 竜摩× 原田, 理代× 鈴木, 堅太郎 |
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| 内容記述 | ||||||
| 内容記述 | Embryonic appendicular structures, such as the limb buds and the developing external genitalia, are suitable models with which to analyze the reciprocal interactions of growth factors in the regulation of outgrowth. Although several studies have evaluated the individual functions of different growth factors in appendicular growth, the coordinated function and integration of input from multiple signaling cascades is poorly understood. We demonstrate that a novel signaling cascade governs formation of the embryonic external genitalia [genital tubercle (GT)]. We show that the dosage of Shh signal is tightly associated with subsequent levels of Wnt/β-catenin activity and the extent of external genitalia outgrowth. In Shh-null mouse embryos, both expression of Wnt ligands and Wnt/β-catenin signaling activity are downregulated. β-catenin gain-of-function mutation rescues defective GT outgrowth and Fgf8 expression in Shh-null embryos. These data indicate that Wnt/β-catenin signaling in the distal urethral epithelium acts downstream of Shh signaling during GT outgrowth. The current data also suggest that Wnt/β-catenin regulates Fgf8 expression via Lef/Tcf binding sites in a 3' conserved enhancer. Fgf8 induces phosphorylation of Erk1/2 and cell proliferation in the GT mesenchyme in vitro, yet Fgf4/8 compound-mutant phenotypes indicate dispensable functions of Fgf4/8 and the possibility of redundancy among multiple Fgfs in GT development. Our results provide new insights into the integration of growth factor signaling in the appendicular developmental programs that regulate external genitalia development. |
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| 書誌情報 |
Development 巻 136, 号 23, p. 3969-3978, 発行年 2009-12-01 |
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| 収録物識別子タイプ | NCID | |||||
| 収録物識別子 | AA10667805 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 関連識別子 | 10.1242/dev.039438 | |||||
| 情報源(ISSN) | ||||||
| 関連名称 | 09501991 | |||||
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| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| 形態 | ||||||
| 1699593 bytes | ||||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 日本十進分類法 | ||||||
| 主題Scheme | NDC | |||||
| 主題 | 491.2 | |||||
| 出版者 | ||||||
| 出版者 | Company of Biologists | |||||
| 資源タイプ | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 論文(Article) | |||||
| 資源タイプ・ローカル | ||||||
| 雑誌掲載論文 | ||||||
| 資源タイプ・NII | ||||||
| Journal Article | ||||||
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| URL | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | http://dev.biologists.org/cgi/content/full/136/23/3969 | |||||
