Reference - Detail
| RRC ID | 72834 |
|---|---|
| Author | Wang S, Tanaka Y, Xu Y, Takeda S, Hirokawa N. |
| Title | KIF3B promotes a PI3K signaling gradient causing changes in a Shh protein gradient and suppressing polydactyly in mice. |
| Journal | Dev Cell |
| Abstract |
Digit determination in limb buds is driven by a posteriorizing Sonic hedgehog (Shh) protein gradient; however, the mechanism regulating this is unclear. Here, we propose a diffusion-and-trapping hypothesis for Shh gradient formation based on data from the preaxial polydactyly phenotype of KIF3B motor hypomorphic mice. In the limb buds of these mice, a distal-to-proximal gradient of fibroblast growth factor (FGF) and phosphatidylinositol 3-kinase (PI3K) signaling and a posterior-to-anterior gradient of Shh were disorganized. This phenotype was reproduced by transplanting FGF8b-soaked beads. At the subcellular level, KIF3B transported the phosphatase and tensin homolog (PTEN)-like phosphatase Talpid3 to terminate PI3K signaling. High and low PI3K signaling strengths differentially sorted endocytosed Shh toward exosome-like particles and cytonemal punctata, respectively. These results indicate that the Shh-containing particles undergo either the diffusional movement in the periphery or cytonemal trapping in the center and form a spatial gradient along the periphery of developing limb buds. |
| Volume | 57(19) |
| Pages | 2273-2289.e11 |
| Published | 2022-10-10 |
| DOI | 10.1016/j.devcel.2022.09.007 |
| PII | S1534-5807(22)00637-2 |
| PMID | 36220081 |
| MeSH | Animals Extremities Fibroblast Growth Factors / metabolism Gene Expression Regulation, Developmental Hedgehog Proteins* / metabolism Kinesins Limb Buds / metabolism Mice Phosphatidylinositol 3-Kinases / genetics Phosphoric Monoester Hydrolases / genetics Polydactyly* / genetics Polydactyly* / metabolism Tensins / genetics Tensins / metabolism |
| IF | 10.092 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 7 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | NIH/3T3(RCB2767) |