Emerging principles of primary cilia dynamics in controlling tissue organization and function

Abstract

Primary cilia project from the surface of most vertebrate cells and are key in sensing extracellular signals and locally transducing this information into a cellular response. Recent findings show that primary cilia are not merely static organelles with a distinct lipid and protein composition. Instead, the function of primary cilia relies on the dynamic composition of molecules within the cilium, the context‐dependent sensing and processing of extracellular stimuli, and cycles of assembly and disassembly in a cell‐ and tissue‐specific manner. Thereby, primary cilia dynamically integrate different cellular inputs and control cell fate and function during tissue development. Here, we review the recently emerging concept of primary cilia dynamics in tissue development, organization, remodeling, and function.

Cilia-mediated cerebrospinal fluid flow modulates neuronal and astroglial activity in the zebrafish larval brain

“…In the zebrafish, the primary cilia of astroglia and neuronal progenitors point toward the CSF-filled ventricles (8,29,100). Since cilia were shown to sense and respond to mechanical stimuli (101), one could hypothesize that primary cilia of astroglia are involved in this process. Taken together, we trust that our findings point to a crucial connection between motile cilia function and glial responses, warranting further investigation into the underlying mechanisms and identifying whether astroglia are regulated by the chemical nature of CSF or mechanical forces exerted by cilia mediate flow.…”

Loss of Bbs8 leads to cystic kidney disease in mice and affects tubulin acetylation through HDAC2

“…Unlike any other organelle, cilia periodically disappear during the mitotic cell cycle: When cells re-enter mitosis, cilia are typically disassembled to subsequently release the basal body, a modified mother centriole, to serve as microtubule organizing centers at the spindle poles. Disassembly of cilia mechanistically involves the deacetylation and thus destabilization of microtubules among others (Pugacheva et al ., 2007; Gopalakrishnan et al ., 2023). It is well established that pathogenetic variants in proteins, which alter the structure or function of cilia, lead to a heterogeneous group of genetic diseases and syndromes referred to as ciliopathies (Hildebrandt, Benzing and Katsanis, 2011).…”

“…Disassembly of cilia mechanistically involves the deacetylation and thus destabilization of microtubules among others (Pugacheva et al, 2007;Gopalakrishnan et al, 2023). It is well established that pathogenetic variants in proteins, which alter the structure or function of cilia, lead to a heterogeneous group of genetic diseases and syndromes referred to as ciliopathies (Hildebrandt, Benzing and Katsanis, 2011).…”

Myocardin-related transcription factor drives epithelial fibrogenesis in polycystic kidney disease

“…PKD is caused by loss-of-function mutations in Polycystin 1 (PC1, encoded by PKD1, 85%) or Polycystin 2 (PC2, encoded by PKD2 , 15%). They can form a heteromultimer and act as chemo- and mechanosensitive complex (Douguet, Patel & Honoré, 2019; Luo et al, 2023), impacting a variety of functions, including cell division and metabolism (Kasahara & Inagaki, 2021; Gopalakrishnan et al, 2023; Wang & Dynlacht, 2018). Histologically, the major features of PKD are fluid-filled cysts and progressive renal fibrosis, which ultimately ruin the kidney architecture, leading to End Stage Renal Disease (ESRD) (Fragiadaki, Macleod & Ong, 2020; Zhang, Reif & Wallace, 2020).…”

“…PKD is caused by loss-of-function mutations in Polycystin 1 (PC1, encoded by PKD1, 85%) or Polycystin 2 (PC2, encoded by PKD2, 15%). They can form a heteromultimer and act as chemo-and mechanosensitive complex (Douguet, Patel & Honoré, 2019;Luo et al, 2023), impacting a variety of functions, including cell division and metabolism (Kasahara & Inagaki, 2021;Gopalakrishnan et al, 2023;Wang & Dynlacht, 2018).…”