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Primary cilia promo...
Primary cilia promote the differentiation of human neurons through the WNT signaling pathway
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- Coschiera, Andrea (author)
- Karolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.
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- Yoshihara, Masahito (author)
- Karolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.;Grad Sch Med, Dept Artificial Intelligence Med, Chiba, Japan.;Chiba Univ, Chiba, Japan.
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- Lauter, Gilbert (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden
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- Ezer, Sini (author)
- Univ Helsinki, Stem Cells & Metab Res Program, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.
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- Pucci, Mariangela (author)
- Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.;Dept Biosci & Technol Food Agr & Environm, Teramo, Italy.;Univ Teramo, Teramo, Italy.
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- Li, Haonan (author)
- Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.
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- Kavsek, Alan (author)
- Karolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.
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- Riedel, Christian G. (author)
- Karolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.
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- Kere, Juha (author)
- Karolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.;Univ Helsinki, Stem Cells & Metab Res Program, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.
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- Swoboda, Peter (author)
- Karolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.
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Karolinska Institutet Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden (creator_code:org_t)
- BioMed Central (BMC), 2024
- 2024
- English.
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In: BMC Biology. - : BioMed Central (BMC). - 1741-7007. ; 22:1
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Abstract
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- BackgroundPrimary cilia emanate from most human cell types, including neurons. Cilia are important for communicating with the cell’s immediate environment: signal reception and transduction to/from the ciliated cell. Deregulation of ciliary signaling can lead to ciliopathies and certain neurodevelopmental disorders. In the developing brain cilia play well-documented roles for the expansion of the neural progenitor cell pool, while information about the roles of cilia during post-mitotic neuron differentiation and maturation is scarce.ResultsWe employed ciliated Lund Human Mesencephalic (LUHMES) cells in time course experiments to assess the impact of ciliary signaling on neuron differentiation. By comparing ciliated and non-ciliated neuronal precursor cells and neurons in wild type and in RFX2 -/- mutant neurons with altered cilia, we discovered an early-differentiation “ciliary time window” during which transient cilia promote axon outgrowth, branching and arborization. Experiments in neurons with IFT88 and IFT172 ciliary gene knockdowns, leading to shorter cilia, confirm these results. Cilia promote neuron differentiation by tipping WNT signaling toward the non-canonical pathway, in turn activating WNT pathway output genes implicated in cyto-architectural changes.ConclusionsWe provide a mechanistic entry point into when and how ciliary signaling coordinates, promotes and translates into anatomical changes. We hypothesize that ciliary alterations causing neuron differentiation defects may result in “mild” impairments of brain development, possibly underpinning certain aspects of neurodevelopmental disorders.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Keyword
- Primary cilia
- WNT signaling
- Neuron differentiation
- Axon branching
- Transcriptomics time-course
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Coschiera, Andre ...
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Yoshihara, Masah ...
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Lauter, Gilbert
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Ezer, Sini
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Pucci, Mariangel ...
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Li, Haonan
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show more...
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Kavsek, Alan
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Riedel, Christia ...
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Kere, Juha
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Swoboda, Peter
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
- Articles in the publication
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BMC Biology
- By the university
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Uppsala University
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Karolinska Institutet