Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hu, Ling, Chen, Yi, Yang, Cui-Ping, Huang, Ying, Song, Ning-Ning, Chen, Jia-Yin, Sun, Yu-Ling, Ding, Yu-Qiang, Lang, Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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
_version_ 1783717943998152704
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
work_keys_str_mv AT huling ulk4anewlydiscoveredsusceptibilitygeneforschizophreniaregulatescorticogenesisinmice
AT chenyi ulk4anewlydiscoveredsusceptibilitygeneforschizophreniaregulatescorticogenesisinmice
AT yangcuiping ulk4anewlydiscoveredsusceptibilitygeneforschizophreniaregulatescorticogenesisinmice
AT huangying ulk4anewlydiscoveredsusceptibilitygeneforschizophreniaregulatescorticogenesisinmice
AT songningning ulk4anewlydiscoveredsusceptibilitygeneforschizophreniaregulatescorticogenesisinmice
AT chenjiayin ulk4anewlydiscoveredsusceptibilitygeneforschizophreniaregulatescorticogenesisinmice
AT sunyuling ulk4anewlydiscoveredsusceptibilitygeneforschizophreniaregulatescorticogenesisinmice
AT dingyuqiang ulk4anewlydiscoveredsusceptibilitygeneforschizophreniaregulatescorticogenesisinmice
AT langbing ulk4anewlydiscoveredsusceptibilitygeneforschizophreniaregulatescorticogenesisinmice