Developmental Cell Article The Graded Response to Sonic Hedgehog Depends on Cilia Architecture

Several studies have linked cilia and Hedgehog signaling, but the precise roles of ciliary pro-teins in signal transduction remain enigmatic. Here we describe a mouse mutation, hennin (hnn), that causes coupled defects in cilia struc-ture and Sonic hedgehog (Shh) signaling. The hnn mutant cilia are short with a specific defect in the structure of the ciliary axoneme, and the hnn neural tube shows a Shh-independent ex-pansion of the domain of motor neuron progen-itors. The hnn mutation is a null allele of Arl13b, a small GTPase of the Arf/Arl family, and the Arl13b protein is localized to cilia. Double mu-tant analysis indicates that Gli3 repressor activ-ity is normal in hnn embryos, but Gli activators are constitutively active at low levels. Thus, nor-mal structure of the ciliary axoneme is required for the cell to translate different levels of Shh ligand into differential regulation of the Gli transcription factors that implement Hedgehog signals