| First Author | Wang S | Year | 2022 |
| Journal | Dev Cell | Volume | 57 |
| Issue | 19 | Pages | 2273-2289.e11 |
| PubMed ID | 36220081 | Mgi Jnum | J:330212 |
| Mgi Id | MGI:7366863 | Doi | 10.1016/j.devcel.2022.09.007 |
| Citation | Wang S, et al. (2022) KIF3B promotes a PI3K signaling gradient causing changes in a Shh protein gradient and suppressing polydactyly in mice. Dev Cell 57(19):2273-2289.e11 |
| abstractText | 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. |
