Roles for IFT172 and Primary Cilia in Cell Migration, Cell Division, and Neocortex Development.

Autor:	Pruski M; Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, China.; National Clinical Research Center for Mental Disorders, Changsha, China.; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.; Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai, China.; School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom., Hu L; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.; School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom., Yang C; Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai, China., Wang Y; Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai, China., Zhang JB; Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, China., Zhang L; Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai, China.; School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom., Huang Y; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.; Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai, China.; School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom., Rajnicek AM; School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom., St Clair D; School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom., McCaig CD; School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom., Lang B; Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, China.; National Clinical Research Center for Mental Disorders, Changsha, China.; School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom., Ding YQ; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.; Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Department of Anatomy and Neurobiology, Collaborative Innovation Centre for Brain Science, Tongji University School of Medicine, Shanghai, China.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2019 Nov 26; Vol. 7, pp. 287. Date of Electronic Publication: 2019 Nov 26 (Print Publication: 2019).
DOI:	10.3389/fcell.2019.00287
Abstrakt:	The cilium of a cell translates varied extracellular cues into intracellular signals that control embryonic development and organ function. The dynamic maintenance of ciliary structure and function requires balanced bidirectional cargo transport involving intraflagellar transport (IFT) complexes. IFT172 is a member of the IFT complex B, and IFT172 mutation is associated with pathologies including short rib thoracic dysplasia, retinitis pigmentosa and Bardet-Biedl syndrome, but how it underpins these conditions is not clear. We used the WIM cell line, derived from embryonic fibroblasts of Wimple mice (carrying homozygous Leu1564Pro mutation in Ift172), to probe roles of Ift172 and primary cilia in cell behavior. WIM cells had ablated cilia and deficiencies in directed migration (electrotaxis), cell proliferation and intracellular signaling. Additionally, WIM cells displayed altered cell cycle progression, with increased numbers of chromatids, highlighting dysfunctional centrosome status. Exposure to a physiological electric field promoted a higher percentage of primary cilia in wild-type cells. Interestingly, in situ hybridization revealed an extensive and dynamic expression profile of Ift172 in both developing and adult mouse cortex. In vivo manipulation of Ift172 expression in germinal regions of embryonic mouse brains perturbed neural progenitor proliferation and radial migration of post-mitotic neurons, revealing a regulatory role of Ift172 in cerebral morphogenesis. Our data suggest that Ift172 regulates a range of fundamental biological processes, highlighting the pivotal roles of the primary cilium in cell physiology and brain development. (Copyright © 2019 Pruski, Hu, Yang, Wang, Zhang, Zhang, Huang, Rajnicek, St Clair, McCaig, Lang and Ding.)
Databáze:	MEDLINE
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