Hedgehog (Hh) is a paracrine signaling protein with major roles in development and disease. In vertebrates and invertebrates, Hh signal transduction is carried out almost entirely by evolutionarily conserved components, and in both, intercellular movement of Hh is mediated by cytonemes - specialized filopodia that serve as bridges that bring distant cells into contact. A significant difference ...

The unexpected connection between cilia and signaling is one of the most exciting developments in cell biology in the past decade. In particular, the Hedgehog (Hh) signaling pathway relies on the primary cilium to regulate tissue patterning and homeostasis in vertebrates. A central question is how ciliary localization and trafficking of Hh pathway components lead to pathway activation and regul...

Recent reports examining the mammalian kinesin relative Kif7 highlight the conserved role for microtubule motor proteins in Drosophila and vertebrate Hedgehog signalling. Mammalian Kif7 action centres at the primary cilium, an organelle absent from Drosophila. These studies raise interesting questions about the coupling of microtubule trafficking to the Hedgehog pathway.

The primary cilium is a biomechanical sensor plugged in at the cell surface. It is implicated in the processing of extracellular signals and its absence or misfunctioning lead to a broad variety of serious defects known as ciliopathies. Unfortunately, the precise mechanisms underlying primary cilium assembly and operation are still poorly understood. Molecular dynamics and intracellular morphog...

Radial glial cells (RCGs) are self-renewing progenitor cells that give rise to neurons and glia during embryonic development. Throughout neurogenesis, these cells contact the cerebral ventricles and bear a primary cilium. Although the role of the primary cilium in embryonic patterning has been studied, its role in brain ventricular morphogenesis is poorly characterized. Using conditional mutant...

The primary cilium is essential for skin morphogenesis through regulating the Notch, Wnt, and hedgehog signaling pathways. Prior studies on the functions of primary cilia in the skin were based on the investigations of genes that are essential for cilium formation. However, none of these ciliogenic genes has been linked to ciliopathy, a group of disorders caused by abnormal formation or functio...

Biallelic inactivation of the von Hippel-Lindau tumor suppressor gene, VHL, occurs in the majority of renal clear cell carcinomas (RCC). VHL's function, regulating the degradation of hypoxia-inducible factor alpha (HIFalpha) subunits, explains the angiogenic nature of these tumors, but not tumor initiation. Because the development of renal cysts precedes tumor formation, and because the dysfunc...

The primary cilium is a ubiquitous organelle present on most mammalian cells. Malfunction of the organelle has been associated with various pathological disorders, many of which lead to cystic disorders in liver, pancreas, and kidney. Primary cilia have in kidney epithelial cells been observed to generate intracellular calcium in response to fluid flow, and disruption of proteins involved in th...

The primary cilium is thought to be disassembled prior to mitosis, freeing the centrosomes to participate in the mitotic spindle. In this issue, Paridaen et al. demonstrate that a remnant of the ciliary membrane remains attached to the mother centriole and is asymmetrically inherited in the developing neocortex.

Various kinases, including a cyclin-dependent kinase (CDK) family member, regulate the growth and functions of primary cilia, which perform essential roles in signaling and development. Neurological disorders linked to CDK-Like (CDKL) proteins suggest that these underexplored kinases may have similar functions. Here, we present the crystal structures of human CDKL1, CDKL2, CDKL3, and CDKL5, rev...