Cargando…

Primary Cilia Dysfunction in Neurodevelopmental Disorders beyond Ciliopathies

Primary cilia are specialized, microtubule-based structures projecting from the surface of most mammalian cells. These organelles are thought to primarily act as signaling hubs and sensors, receiving and integrating extracellular cues. Several important signaling pathways are regulated through the p...

Descripción completa

Detalles Bibliográficos
Autores principales: Karalis, Vasiliki, Donovan, Kathleen E., Sahin, Mustafa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782889/
https://www.ncbi.nlm.nih.gov/pubmed/36547476
http://dx.doi.org/10.3390/jdb10040054
_version_ 1784857446310739968
author Karalis, Vasiliki
Donovan, Kathleen E.
Sahin, Mustafa
author_facet Karalis, Vasiliki
Donovan, Kathleen E.
Sahin, Mustafa
author_sort Karalis, Vasiliki
collection PubMed
description Primary cilia are specialized, microtubule-based structures projecting from the surface of most mammalian cells. These organelles are thought to primarily act as signaling hubs and sensors, receiving and integrating extracellular cues. Several important signaling pathways are regulated through the primary cilium including Sonic Hedgehog (Shh) and Wnt signaling. Therefore, it is no surprise that mutated genes encoding defective proteins that affect primary cilia function or structure are responsible for a group of disorders collectively termed ciliopathies. The severe neurologic abnormalities observed in several ciliopathies have prompted examination of primary cilia structure and function in other brain disorders. Recently, neuronal primary cilia defects were observed in monogenic neurodevelopmental disorders that were not traditionally considered ciliopathies. The molecular mechanisms of how these genetic mutations cause primary cilia defects and how these defects contribute to the neurologic manifestations of these disorders remain poorly understood. In this review we will discuss monogenic neurodevelopmental disorders that exhibit cilia deficits and summarize findings from studies exploring the role of primary cilia in the brain to shed light into how these deficits could contribute to neurologic abnormalities.
format Online
Article
Text
id pubmed-9782889
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-97828892022-12-24 Primary Cilia Dysfunction in Neurodevelopmental Disorders beyond Ciliopathies Karalis, Vasiliki Donovan, Kathleen E. Sahin, Mustafa J Dev Biol Review Primary cilia are specialized, microtubule-based structures projecting from the surface of most mammalian cells. These organelles are thought to primarily act as signaling hubs and sensors, receiving and integrating extracellular cues. Several important signaling pathways are regulated through the primary cilium including Sonic Hedgehog (Shh) and Wnt signaling. Therefore, it is no surprise that mutated genes encoding defective proteins that affect primary cilia function or structure are responsible for a group of disorders collectively termed ciliopathies. The severe neurologic abnormalities observed in several ciliopathies have prompted examination of primary cilia structure and function in other brain disorders. Recently, neuronal primary cilia defects were observed in monogenic neurodevelopmental disorders that were not traditionally considered ciliopathies. The molecular mechanisms of how these genetic mutations cause primary cilia defects and how these defects contribute to the neurologic manifestations of these disorders remain poorly understood. In this review we will discuss monogenic neurodevelopmental disorders that exhibit cilia deficits and summarize findings from studies exploring the role of primary cilia in the brain to shed light into how these deficits could contribute to neurologic abnormalities. MDPI 2022-12-13 /pmc/articles/PMC9782889/ /pubmed/36547476 http://dx.doi.org/10.3390/jdb10040054 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Karalis, Vasiliki
Donovan, Kathleen E.
Sahin, Mustafa
Primary Cilia Dysfunction in Neurodevelopmental Disorders beyond Ciliopathies
title Primary Cilia Dysfunction in Neurodevelopmental Disorders beyond Ciliopathies
title_full Primary Cilia Dysfunction in Neurodevelopmental Disorders beyond Ciliopathies
title_fullStr Primary Cilia Dysfunction in Neurodevelopmental Disorders beyond Ciliopathies
title_full_unstemmed Primary Cilia Dysfunction in Neurodevelopmental Disorders beyond Ciliopathies
title_short Primary Cilia Dysfunction in Neurodevelopmental Disorders beyond Ciliopathies
title_sort primary cilia dysfunction in neurodevelopmental disorders beyond ciliopathies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782889/
https://www.ncbi.nlm.nih.gov/pubmed/36547476
http://dx.doi.org/10.3390/jdb10040054
work_keys_str_mv AT karalisvasiliki primaryciliadysfunctioninneurodevelopmentaldisordersbeyondciliopathies
AT donovankathleene primaryciliadysfunctioninneurodevelopmentaldisordersbeyondciliopathies
AT sahinmustafa primaryciliadysfunctioninneurodevelopmentaldisordersbeyondciliopathies