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Abstract Hedgehog (Hh) signaling relies on the primary cilium, a cell surface organelle that serves as a signaling hub for the cell. Using proximity labeling and quantitative proteomics, we identify Numb as a ciliary protein that positively regulates Hh signaling. Numb localizes to the ciliary pocket and acts as an endocytic adaptor to incorporate Ptch1 into clathrin-coated vesicles, thereby promoting Ptch1 exit from the cilium, a key step in Hh signaling activation. Numb loss impedes Sonic hedgehog (Shh)-induced Ptch1 exit from the cilium, resulting in reduced Hh signaling. Numb loss in spinal neural progenitors reduces Shh-induced differentiation into cell fates reliant on high Hh activity. Genetic ablation of Numb in the developing cerebellum impairs the proliferation of granule cell precursors, a Hh-dependent process, resulting in reduced cerebellar size. This study highlights Numb as a regulator of ciliary Ptch1 levels during Hh signal activation and demonstrates the key role of ciliary pocket-mediated endocytosis in cell signaling. 

X-ray photoelectron spectroscopy (XPS), ultraviolet photoelectron spectroscopy (UPS), atomic force microscopy (AFM) and X-ray diffraction (XRD) were applied to investigate the electronic structure and molecular packing of C8-BTBT on HOPG with an ultrathin C 60 interlayer. It was found that C8-BTBT displays a Vollmer–Weber (V–W) growth mode on HOPG, with an ultrathin C 60 interlayer (0.7 nm). Compared to the uniform lying-down growth mode as directly grown on HOPG, the C8-BTBT molecules here adopt a lying-down orientation at low coverage with some small tilt angles because the π–π interaction between C8-BTBT and HOPG is partly disturbed by the C 60 interlayer, delivering a higher highest occupied molecular orbital (HOMO) in C8-BTBT. An interface dipole of 0.14 eV is observed due to electron transport from C8-BTBT to C 60 . The upward and downward band bending in C8-BTBT and C 60 , respectively, near the C8-BTBT/C 60 interface reduces the hole transport barrier at the interface, facilitating the hole injection from C 60 to C8-BTBT, while a large electron transfer barrier from C 60 to C8-BTBT is detected at this interface, which effectively limits electron injection from C 60 to C8-BTBT. The HOMO of C8-BTBT near the interface is largely lifted up by the C 60 insertion layer, which causes a p-doping effect and increases the hole mobility in C8-BTBT. Furthermore, owing to the lowest occupied molecular orbital (LUMO) of C 60 residing in the gap of C8-BTBT, charge transfer occurs between C 60 and the trap states in C8-BTBT to effectively passivate the trapping states. Our efforts aid a better understanding of the electron structure and film growth of anisotropic molecules and provide a useful strategy to improve the performance of C8-BTBT-based devices.