Cellular signalling by primary cilia in development, organ function and disease

Abstract

Primary cilia project in a single copy from the surface of most vertebrate cell types; they detect and transmit extracellular cues to regulate diverse cellular processes during development and to maintain tissue homeostasis. The sensory capacity of primary cilia relies on the coordinated trafficking and temporal localization of specific receptors and associated signal transduction modules in the cilium. The canonical hedgehog (HH) pathway, for example, is a bona fide ciliary signalling system that regulates cell fate and self-renewal in development and tissue homeostasis. Specific receptors and associated signal transduction proteins can also localize to primary cilia in a cell type-dependent manner; available evidence suggests that the ciliary constellation of these proteins can temporally change to allow the cell to adapt to specific developmental and homeostatic cues. Consistent with important roles for primary cilia in signalling, mutations that lead to their dysfunction underlie a pleiotropic group of diseases and syndromic disorders termed ciliopathies, which affect many different tissues and organs of the body. In this review we highlight central mechanisms by which primary cilia coordinate HH, G-protein-coupled receptor, WNT, receptor tyrosine kinase and TGFβ/BMP signalling, and illustrate how defects in the balanced output of ciliary signalling events are coupled to developmental disorders and disease progression. Opening section The primary cilium is a microtubule-based, non-motile organelle that extends as a solitary unit from the basal body (derived from the centrosomal mother centriole of most cell types

Elevated miR‐200a and miR‐141 inhibit endocrine gland‐derived vascular endothelial growth factor expression and ciliogenesis in preeclampsia

“…; Anvarian et al . ). Defects in ciliary structure or abnormal ciliary functions lead to complex human diseases (ciliopathies), including polycystic kidney disease, skeletal malformation, primarily retinal degeneration, and several types of cancers, such as medulloblastoma and basal cell carcinoma (Bangs et al .…”

“…; Anvarian et al . ). Cilia are also crucial for spatial placement during organ development of mouse embryo (Nonaka et al .…”

“…During human early pregnancy, the EG-VEGF receptor PROKR1 is mainly expressed on the primary cilia, where EG-VEGF triggers downstream signalling to facilitate trophoblast invasion (Wang et al 2017). Primary cilia are microtubule-based structures that extend from the surface of most vertebrate cell types, and they detect and transmit extracellular environmental signals into cells for regulating development and maintaining tissue homeostasis (Werner et al 2017;Anvarian et al 2019). Defects in ciliary structure or abnormal ciliary functions lead to complex human diseases (ciliopathies), including polycystic kidney disease, skeletal malformation, primarily retinal degeneration, and several types of cancers, such as medulloblastoma and basal cell carcinoma (Bangs et al 2017;Anvarian et al 2019).…”

“…Primary cilia are microtubule-based structures that extend from the surface of most vertebrate cell types, and they detect and transmit extracellular environmental signals into cells for regulating development and maintaining tissue homeostasis (Werner et al 2017;Anvarian et al 2019). Defects in ciliary structure or abnormal ciliary functions lead to complex human diseases (ciliopathies), including polycystic kidney disease, skeletal malformation, primarily retinal degeneration, and several types of cancers, such as medulloblastoma and basal cell carcinoma (Bangs et al 2017;Anvarian et al 2019). Cilia are also crucial for spatial placement during organ development of mouse embryo (Nonaka et al 1998;Yoshiba et al 2012), and some factors expressed on the cilia of the placental fetal portion may act as a growth factor for the trophoblasts during the peri-implantation period (Grosso et al 2015).…”

ESCRT subunit CHMP4B localizes to primary cilia and is required for the structural integrity of the ciliary membrane

“…1,2 Malfunction of primary cilia is associated with a series of human genetic disorders collectively called the ciliopathies. Primary cilia serve as a cellular antenna transmitting chemical or mechanical stimuli, and also play an essential role in coordinating various signaling pathways required for the development and maintenance of multiple organs and tissues.…”