Chapter 9 The Primary Cilium: At the Crossroads of Mammalian Hedgehog Signaling

Abstract

Cilia function as critical sensors of extracellular information, and ciliary dysfunction underlies diverse human disorders including situs inversus, polycystic kidney disease, retinal degeneration, and Bardet-Biedl syndrome. Importantly, mammalian primary cilia have recently been shown to mediate transduction of Hedgehog (Hh) signals, which are involved in a variety of developmental processes. Mutations in several ciliary components disrupt the patterning of the neural tube and limb bud, tissues that rely on precisely coordinated gradients of Hh signal transduction. Numerous components of the Hh pathway, including Patched, Smoothened, and the Gli transcription factors, are present within primary cilia, indicating that key steps of Hh signaling may occur within the cilium. Because dysregulated Hh signaling promotes the development of a variety of human tumors, cilia may also have roles in cancer. Together, these findings have shed light on one mechanism by which primary cilia transduce signals critical for both development and disease.