A cell-autonomous role for primary cilia in long-range commissural axon guidance

Dumoulin, Alexandre; Wilson, Nicole H.; Tucker, Kerry L.; Stoeckli, Esther T.

doi:10.1101/2022.08.15.503894

Cited by 3 publications

(2 citation statements)

References 57 publications

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“…Perturbations to Shh activity also result in abnormal migration, implicating Shh signaling as an important ciliary signal during interneuron migration (Baudoin et al, 2012). Commissural axon pathfinding is impaired following disruptions to ciliary proteins which is consistent with cilia playing an important role in axon guidance (Dumoulin et al, 2022;Ferent et al, 2019;Suciu & Caspary, 2021). Thus, cilia regulate key cellular processes that build the nervous system.…”

Section: Mouse Models Reveal Cilia Are Key Regulators Of Neuron Devel...mentioning

confidence: 55%

Uncovering cilia function in glial development

Bear

Caspary

2023

Annals of Human Genetics

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SUMMARYPrimary cilia play critical roles in regulating signaling pathways that underlie several developmental processes. In the nervous system, cilia are known to regulate signals that guide neuron development. Cilia dysregulation is implicated in neurological diseases, and the underlying mechanisms remain poorly understood. Cilia research has predominantly focused on neurons and has overlooked the diverse population of glial cells in the brain. Glial cells play essential roles during neurodevelopment, and their dysfunction contributes to neurological disease; however, the relationship between cilia function and glial development is understudied. Here we review the state of the field and highlight the glial cell types where cilia are found and the ciliary functions that are linked to glial development. This work uncovers the importance of cilia in glial development and raises outstanding questions for the field. We are poised to make progress in understanding the function of glial cilia in human development and their contribution to neurological diseases.

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Section: Mouse Models Reveal Cilia Are Key Regulators Of Neuron Devel...mentioning

confidence: 55%

Uncovering cilia function in glial development

Bear

Caspary

2023

Annals of Human Genetics

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“…A precedent for cilium-dependent long-range control of biological events at remote terminal processes is afforded by examination of axonal pathfinding in embryonic neurons in the chick and the mouse. Axonal growth cones of neurons crossing the ventral midline of the spinal cord were found to employ retrograde transport of midline-derived Shh for activation of Hh signaling cascades at the primary cilium on the cell body of the same neuron, localized at the neuronal soma, hundreds of cell diameters away 67 . Similarly, retinal ganglion cells have been reported to use anterograde transport of Shh to the optic chiasm, where secretion could direct axonal outgrowth 68 .…”

Section: Discussionmentioning

confidence: 99%

The Primary Cilium and its Hedgehog Signaling in Nociceptors Contribute to Inflammatory and Neuropathic Pain

Fitzsimons,

Staurengo-Ferrari,

Bogen

et al. 2023

Preprint

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The primary cilium, a 1-3 μm long hair-like structure protruding from the surface of almost all cells in the vertebrate body, is critical for neuronal development and also functions in the adult. As the migratory neural crest settles into dorsal root ganglia (DRG) sensory neurons elaborate a single primary cilium at their soma that is maintained into adult stages. While it is not known if primary cilia are expressed in nociceptors, or their potential function in the mature DRG neuron, recent studies have shown a role for Hedgehog, whose signaling demonstrates a dependence on primary cilia, in nociceptor sensitization. Here we report the expression of primary cilia in rat and mouse nociceptors, where they modulate mechanical nociceptive threshold, and contribute to inflammatory and neuropathic pain. When siRNA targetingIft88, a primary cilium-specific intra-flagellar transport (IFT) protein required for ciliary integrity, was administered by intrathecal injection, in the rat, it resulted in loss ofIft88mRNA in DRG, and primary cilia in neuronal cell bodies, which was associated with an increase in mechanical nociceptive threshold, and abrogation of hyperalgesia induced by the pronociceptive inflammatory mediator, prostaglandin E2, and painful peripheral neuropathy induced by a neurotoxic chemotherapy drug, paclitaxel. To provide further support for the role of the primary cilium in nociceptor function we also administered siRNA for another IFT protein,Ift52.Ift52 siRNA results in loss ofIft52 in DRG and abrogates paclitaxel-induced painful peripheral neuropathy. Attenuation of Hedgehog-induced hyperalgesia byIft88knockdown supports a role for the primary cilium in the hyperalgesia induced by Hedgehog, and attenuation of paclitaxel chemotherapy-induced neuropathy (CIPN) by cyclopamine, which attenuates Hedgehog signaling, suggests a role of Hedgehog in CIPN. Our findings support a role of nociceptor primary cilia in the control of mechanical nociceptive threshold and in inflammatory and neuropathic pain, the latter, at least in part, Hedgehog dependent.

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An Emerging Role for Primary Cilia of the Renal Glomerulus: Implications and Considerations for Pathogenesis of Glomerular Diseases

Fitzsimons

2024

Physiology

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Primary cilia are highly specialized, sensory protrusions elaborated from nearly all eukaryotic cells. Our knowledge of their structure and function continues to evolve, driven by an expanding clinical prevalence of human diseases causally linked to primary cilia-specific, genetic mutations. Such mutations often lead to the translation of malformed, non-functional or even absent ciliary proteins, damage the structural integrity of and/or prevent the elaboration of the cilium entirely, and lead to a spectrum of congenital abnormalities/diseases, termed ciliopathies. In the kidneys, genetic mutations linked to primary cilia cause nephronophthisis, autosomal dominant and recessive polycystic kidney diseases, and even renal carcinoma. However, documentation of primary cilia, specific to the glomerulus (the spherical, filtering/functional unit of the nephron), remains scarce and is poorly understood. As such, many chronic kidney diseases, notably glomerular diseases, lack characterization/acknowledgment of primary cilia as instigators of, and/or even reno-protective target effectors mediating many of the molecular disease processes involved therein. The following chapter will provide an up-to-date, comprehensive summary of primary cilia from relevant glomerular cell types, discuss novel implications for future study to improve our understanding of glomerular diseases, and provide a body of evidence in support for the development/efficacy of future therapies/treatments targeting glomerular primary cilia.

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A cell-autonomous role for primary cilia in long-range commissural axon guidance

Cited by 3 publications

References 57 publications

Uncovering cilia function in glial development

Uncovering cilia function in glial development

The Primary Cilium and its Hedgehog Signaling in Nociceptors Contribute to Inflammatory and Neuropathic Pain

An Emerging Role for Primary Cilia of the Renal Glomerulus: Implications and Considerations for Pathogenesis of Glomerular Diseases

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