Developmental and regenerative paradigms of cilia regulated hedgehog signaling.

Seminars in Cell & Developmental Biology
Daniel KopinkeSaikat Mukhopadhyay

Abstract

Primary cilia are immotile appendages that have evolved to receive and interpret a variety of different extracellular cues. Cilia play crucial roles in intercellular communication during development and defects in cilia affect multiple tissues accounting for a heterogeneous group of human diseases called ciliopathies. The Hedgehog (Hh) signaling pathway is one of these cues and displays a unique and symbiotic relationship with cilia. Not only does Hh signaling require cilia for its function but the majority of the Hh signaling machinery is physically located within the cilium-centrosome complex. More specifically, cilia are required for both repressing and activating Hh signaling by modifying bifunctional Gli transcription factors into repressors or activators. Defects in balancing, interpreting or establishing these repressor/activator gradients in Hh signaling either require cilia or phenocopy disruption of cilia. Here, we will summarize the current knowledge on how spatiotemporal control of the molecular machinery of the cilium allows for a tight control of basal repression and activation states of the Hh pathway. We will then discuss several paradigms on how cilia influence Hh pathway activity in tissue morphogenesis during...Continue Reading

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Citations

Feb 20, 2021·Frontiers in Cell and Developmental Biology·Kerstin Hasenpusch-Theil, Thomas Theil
Jun 5, 2021·Scientific Reports·Ariel WaismanDaniel Kopinke
Jun 1, 2021·Frontiers in Cell and Developmental Biology·Marijn F StokmanAlexandre Benmerah
Jun 11, 2021·Biochemical Pharmacology·Vikas DaggubatiNavdar Sever
Aug 8, 2021·Seminars in Cell & Developmental Biology·Megan L Killian
Dec 7, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Liwei ZhangJianquan Chen
Jan 11, 2022·The Journal of Cell Biology·Bryony BraschiStephen M King

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