Primary cilia: cellular sensors for the skeleton

Abstract

The primary cilium is a solitary, immotile cilium that is present in almost every mammalian cell type. Primary cilia are thought to function as chemosensors, mechanosensors, or both, depending on cell type, and have been linked to several developmental signaling pathways. Primary cilium malfunction has been implicated in several human diseases, the symptoms of which include vision and hearing loss, polydactyly, and polycystic kidneys. Recently, primary cilia have also been implicated in the development and homeostasis of the skeleton. In this review, we discuss the structure and formation of the primary cilium and some of the mechanical and chemical signals to which it could be sensitive, with a focus on skeletal biology. We also raise several unanswered questions regarding the role of primary cilia as mechanosensors and chemosensors and identify potential research avenues to address these questions.

Fig. 1

Schematic of primary cilium structure. The primary cilium is enclosed in a specialized membrane (dark green) that is continuous with the plasma membrane (light green). Membranes are shown in cutaway view. The axoneme of the primary cilium (dark blue) extends from the mother centriole/basal body (purple), which possesses subdistal appendages (orange) that are connected to a subset of cytoplasmic microtubules (red). The mother centriole/basal body is part of the centrosome, which includes a daughter centriole (light blue) and pericentriolar material (light gray) from which other cytoplasmic microtubules (red) are nucleated). The mother centriole/basal body is connected to the plasma membrane via transition fibers (yellow) that separate the ciliary compartment from the cytoplasm. Cytoplasmic microtubules are reduced in number and shortened for simplicity; they actually extend far beyond the boundaries of the image. Image not to scale.