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- W4304014114 endingPage "2289.e11" @default.
- W4304014114 startingPage "2273" @default.
- W4304014114 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." @default.
- W4304014114 created "2022-10-10" @default.
- W4304014114 creator A5005018064 @default.
- W4304014114 creator A5030524373 @default.
- W4304014114 creator A5051434566 @default.
- W4304014114 creator A5065735206 @default.
- W4304014114 creator A5083955309 @default.
- W4304014114 date "2022-10-01" @default.
- W4304014114 modified "2023-10-16" @default.
- W4304014114 title "KIF3B promotes a PI3K signaling gradient causing changes in a Shh protein gradient and suppressing polydactyly in mice" @default.
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