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Promyelocytic leukemia zinc finger is involved in the formation of deep layer cortical neurons

BACKGROUND: Promyelocytic leukemia zinc finger (Plzf), a transcriptional regulator involved in a lot of important biological processes during development, has been implied to maintain neural stem cells and inhibit their differentiation into neurons. However, the effects of Plzf on brain structures a...

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Autores principales: Lin, Hsin-Chuan, Ching, Yung-Hao, Huang, Chi-Chen, Pao, Ping-Chieh, Lee, Yi-Hua, Chang, Wen-Chang, Kao, Tzu-Jen, Lee, Yi-Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485146/
https://www.ncbi.nlm.nih.gov/pubmed/31027502
http://dx.doi.org/10.1186/s12929-019-0519-8
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author Lin, Hsin-Chuan
Ching, Yung-Hao
Huang, Chi-Chen
Pao, Ping-Chieh
Lee, Yi-Hua
Chang, Wen-Chang
Kao, Tzu-Jen
Lee, Yi-Chao
author_facet Lin, Hsin-Chuan
Ching, Yung-Hao
Huang, Chi-Chen
Pao, Ping-Chieh
Lee, Yi-Hua
Chang, Wen-Chang
Kao, Tzu-Jen
Lee, Yi-Chao
author_sort Lin, Hsin-Chuan
collection PubMed
description BACKGROUND: Promyelocytic leukemia zinc finger (Plzf), a transcriptional regulator involved in a lot of important biological processes during development, has been implied to maintain neural stem cells and inhibit their differentiation into neurons. However, the effects of Plzf on brain structures and functions are still not clarified. RESULTS: We showed that Plzf expression was detected as early as embryonic day (E) 9.5 in Pax6(+) cells in the mouse brain, and was completely disappeared in telencephalon before the initiation of cortical neurogenesis. Loss of Plzf resulted in a smaller cerebral cortex with a decrease in the number of Tbr1(+) deep layer neurons due to a decrease of mitotic cell number in the ventricular zone of forebrain at early developmental stage. Microarray, qRT-PCR, and flow cytometry analysis identified dysregulation of Mash1 proneural gene expression. We also observed an impairment of recognition memory in Plzf-deficient mice. CONCLUSIONS: Plzf is expressed at early stages of brain development and involved in the formation of deep layer cortical neurons. Loss of Plzf results in dysregulation of Mash1, microcephaly with reduced numbers of early-born neurons, and impairment of recognition memory. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12929-019-0519-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-64851462019-05-03 Promyelocytic leukemia zinc finger is involved in the formation of deep layer cortical neurons Lin, Hsin-Chuan Ching, Yung-Hao Huang, Chi-Chen Pao, Ping-Chieh Lee, Yi-Hua Chang, Wen-Chang Kao, Tzu-Jen Lee, Yi-Chao J Biomed Sci Research BACKGROUND: Promyelocytic leukemia zinc finger (Plzf), a transcriptional regulator involved in a lot of important biological processes during development, has been implied to maintain neural stem cells and inhibit their differentiation into neurons. However, the effects of Plzf on brain structures and functions are still not clarified. RESULTS: We showed that Plzf expression was detected as early as embryonic day (E) 9.5 in Pax6(+) cells in the mouse brain, and was completely disappeared in telencephalon before the initiation of cortical neurogenesis. Loss of Plzf resulted in a smaller cerebral cortex with a decrease in the number of Tbr1(+) deep layer neurons due to a decrease of mitotic cell number in the ventricular zone of forebrain at early developmental stage. Microarray, qRT-PCR, and flow cytometry analysis identified dysregulation of Mash1 proneural gene expression. We also observed an impairment of recognition memory in Plzf-deficient mice. CONCLUSIONS: Plzf is expressed at early stages of brain development and involved in the formation of deep layer cortical neurons. Loss of Plzf results in dysregulation of Mash1, microcephaly with reduced numbers of early-born neurons, and impairment of recognition memory. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12929-019-0519-8) contains supplementary material, which is available to authorized users. BioMed Central 2019-04-26 /pmc/articles/PMC6485146/ /pubmed/31027502 http://dx.doi.org/10.1186/s12929-019-0519-8 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Lin, Hsin-Chuan
Ching, Yung-Hao
Huang, Chi-Chen
Pao, Ping-Chieh
Lee, Yi-Hua
Chang, Wen-Chang
Kao, Tzu-Jen
Lee, Yi-Chao
Promyelocytic leukemia zinc finger is involved in the formation of deep layer cortical neurons
title Promyelocytic leukemia zinc finger is involved in the formation of deep layer cortical neurons
title_full Promyelocytic leukemia zinc finger is involved in the formation of deep layer cortical neurons
title_fullStr Promyelocytic leukemia zinc finger is involved in the formation of deep layer cortical neurons
title_full_unstemmed Promyelocytic leukemia zinc finger is involved in the formation of deep layer cortical neurons
title_short Promyelocytic leukemia zinc finger is involved in the formation of deep layer cortical neurons
title_sort promyelocytic leukemia zinc finger is involved in the formation of deep layer cortical neurons
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485146/
https://www.ncbi.nlm.nih.gov/pubmed/31027502
http://dx.doi.org/10.1186/s12929-019-0519-8
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