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Ulk4, a Newly Discovered Susceptibility Gene for Schizophrenia, Regulates Corticogenesis in Mice
Schizophrenia (SCZ) is a chronic and severe mental disease that affects around 1% of the population. The precise etiology of SCZ still remains largely unknown, and no conclusive mechanisms are firmly established. Recent advances in epidemiological and clinical investigation support an overwhelmingly...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255617/ https://www.ncbi.nlm.nih.gov/pubmed/34235142 http://dx.doi.org/10.3389/fcell.2021.645368 |
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author | Hu, Ling Chen, Yi Yang, Cui-Ping Huang, Ying Song, Ning-Ning Chen, Jia-Yin Sun, Yu-Ling Ding, Yu-Qiang Lang, Bing |
author_facet | Hu, Ling Chen, Yi Yang, Cui-Ping Huang, Ying Song, Ning-Ning Chen, Jia-Yin Sun, Yu-Ling Ding, Yu-Qiang Lang, Bing |
author_sort | Hu, Ling |
collection | PubMed |
description | Schizophrenia (SCZ) is a chronic and severe mental disease that affects around 1% of the population. The precise etiology of SCZ still remains largely unknown, and no conclusive mechanisms are firmly established. Recent advances in epidemiological and clinical investigation support an overwhelmingly strong neurodevelopmental origin for SCZ. Here, we demonstrated that Unc-51-like kinase 4 (Ulk4), a novel risk factor for major mental disorders including schizophrenia, is involved in the corticogenesis. Deletion of Ulk4 in mice led to significantly thinner layers of II–III, and V in the cerebral cortex, which was confirmed in conditional Ulk4 deletion mice achieved by Cre-loxp strategy. This abnormality might be caused by decreased intermediate neural progenitors and increased apoptosis. Thus, our data suggest that Ulk4 manipulates the behaviors of neural progenitors during brain development and, when functionally defective, leads to the reduction of specific cortical layers. This anomaly may increase predisposition to a range of neurodevelopmental disorders, including SCZ. |
format | Online Article Text |
id | pubmed-8255617 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82556172021-07-06 Ulk4, a Newly Discovered Susceptibility Gene for Schizophrenia, Regulates Corticogenesis in Mice Hu, Ling Chen, Yi Yang, Cui-Ping Huang, Ying Song, Ning-Ning Chen, Jia-Yin Sun, Yu-Ling Ding, Yu-Qiang Lang, Bing Front Cell Dev Biol Cell and Developmental Biology Schizophrenia (SCZ) is a chronic and severe mental disease that affects around 1% of the population. The precise etiology of SCZ still remains largely unknown, and no conclusive mechanisms are firmly established. Recent advances in epidemiological and clinical investigation support an overwhelmingly strong neurodevelopmental origin for SCZ. Here, we demonstrated that Unc-51-like kinase 4 (Ulk4), a novel risk factor for major mental disorders including schizophrenia, is involved in the corticogenesis. Deletion of Ulk4 in mice led to significantly thinner layers of II–III, and V in the cerebral cortex, which was confirmed in conditional Ulk4 deletion mice achieved by Cre-loxp strategy. This abnormality might be caused by decreased intermediate neural progenitors and increased apoptosis. Thus, our data suggest that Ulk4 manipulates the behaviors of neural progenitors during brain development and, when functionally defective, leads to the reduction of specific cortical layers. This anomaly may increase predisposition to a range of neurodevelopmental disorders, including SCZ. Frontiers Media S.A. 2021-06-21 /pmc/articles/PMC8255617/ /pubmed/34235142 http://dx.doi.org/10.3389/fcell.2021.645368 Text en Copyright © 2021 Hu, Chen, Yang, Huang, Song, Chen, Sun, Ding and Lang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Hu, Ling Chen, Yi Yang, Cui-Ping Huang, Ying Song, Ning-Ning Chen, Jia-Yin Sun, Yu-Ling Ding, Yu-Qiang Lang, Bing Ulk4, a Newly Discovered Susceptibility Gene for Schizophrenia, Regulates Corticogenesis in Mice |
title | Ulk4, a Newly Discovered Susceptibility Gene for Schizophrenia, Regulates Corticogenesis in Mice |
title_full | Ulk4, a Newly Discovered Susceptibility Gene for Schizophrenia, Regulates Corticogenesis in Mice |
title_fullStr | Ulk4, a Newly Discovered Susceptibility Gene for Schizophrenia, Regulates Corticogenesis in Mice |
title_full_unstemmed | Ulk4, a Newly Discovered Susceptibility Gene for Schizophrenia, Regulates Corticogenesis in Mice |
title_short | Ulk4, a Newly Discovered Susceptibility Gene for Schizophrenia, Regulates Corticogenesis in Mice |
title_sort | ulk4, a newly discovered susceptibility gene for schizophrenia, regulates corticogenesis in mice |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255617/ https://www.ncbi.nlm.nih.gov/pubmed/34235142 http://dx.doi.org/10.3389/fcell.2021.645368 |
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