| RRC ID |
72834
|
| 著者 |
Wang S, Tanaka Y, Xu Y, Takeda S, Hirokawa N.
|
| タイトル |
KIF3B promotes a PI3K signaling gradient causing changes in a Shh protein gradient and suppressing polydactyly in mice.
|
| ジャーナル |
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.
|
| 巻・号 |
57(19)
|
| ページ |
2273-2289.e11
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
NIH/3T3(RCB2767) |
