論文 - 詳細
| RRC ID | 86102 |
|---|---|
| 著者 | Wu S, Bian Y, Zhang C, Liu K, Sun F, Chen E, Zhou C, Yu L, Chen G, Wu M. |
| タイトル | Merlin controls limb development and thumb formation by regulating primary cilium-hedgehog signaling. |
| ジャーナル | Cell Rep |
| Abstract |
Hedgehog (HH) signaling, transduced at the primary cilium, plays a crucial role in limb longitudinal growth and digit formation, but its involvement in thumb development has been underestimated. This study identifies Merlin (Nf2) as a critical regulator of limb development, modulating the ciliary trafficking of the HH receptor, Smoothened. Merlin is predominantly expressed in limb buds and growth plates. Conditional knockout of Merlin in limb mesenchyme in mice results in dwarfism, brachydactyly, and thumb hypoplasia, with transcriptomic profiling and molecular analyses revealing disrupted HH signaling. Mechanistically, Merlin interacts with ARF6 to regulate the ciliary transport of Smoothened via RAB11+ vesicles. Importantly, pharmacological enhancement of HH signaling significantly corrected the limb defects caused by Merlin deletion. These findings highlight the essential role of Merlin in regulating longitudinal limb growth and thumb morphogenesis via primary cilium-HH signaling, suggesting potential therapeutic strategies for related limb dysplasias. |
| 巻・号 | 44(6) |
| ページ | 115849 |
| 公開日 | 2025-6-24 |
| DOI | 10.1016/j.celrep.2025.115849 |
| PII | S2211-1247(25)00620-5 |
| PMID | 40503937 |
| MeSH | ADP-Ribosylation Factors / metabolism Animals Cilia* / metabolism Extremities* / embryology Hedgehog Proteins* / metabolism Humans Limb Buds / metabolism Mice Mice, Knockout Neurofibromin 2* / genetics Neurofibromin 2* / metabolism Signal Transduction* Smoothened Receptor / metabolism Thumb* / embryology |
| IF | 8.109 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |