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Fzr/Cdh1 Promotes the Differentiation of Neural Stem Cell Lineages in Drosophila

How stem cells and progenitors balance between self-renewal and differentiation is a central issue of stem cell biology. Here, we describe a novel and essential function of Drosophila Fzr/Cdh1, an evolutionary conserved protein, during the differentiation of neural stem cell (NSC) lineages in the ce...

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Autores principales: Ly, Phuong Thao, Wang, Hongyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026481/
https://www.ncbi.nlm.nih.gov/pubmed/32117986
http://dx.doi.org/10.3389/fcell.2020.00060
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author Ly, Phuong Thao
Wang, Hongyan
author_facet Ly, Phuong Thao
Wang, Hongyan
author_sort Ly, Phuong Thao
collection PubMed
description How stem cells and progenitors balance between self-renewal and differentiation is a central issue of stem cell biology. Here, we describe a novel and essential function of Drosophila Fzr/Cdh1, an evolutionary conserved protein, during the differentiation of neural stem cell (NSC) lineages in the central nervous system. We show that Fzr, a known co-activator of Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase, promotes the production of neurons from neural progenitors called ganglion mother cells (GMCs). However, knockdown of APC/C subunit Ida or another APC/C co-activator CDC20 does not similarly impair GMC-neuron transition. We also observe a concomitant loss of differentiation factor Prospero expression and ectopic accumulation of mitotic kinase Polo in fzr mutant clones, strongly supporting the impairment of GMC to neuron differentiation. Besides functioning in GMCs, Fzr is also present in NSCs to facilitate the production of intermediate neural progenitors from NSCs. Taken together, Fzr plays a novel function in promoting differentiation programs during Drosophila NSC lineage development. Given that human Fzr is inactivated in multiple types of human cancers including brain tumors and that Fzr regulates neurotoxicity in various models of neurodegenerative diseases, our study on the role of Fzr in turning off proliferation in neuronal cells may provide insights into how Fzr deficits may contribute to human neurodegenerative diseases and tumors.
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spelling pubmed-70264812020-02-28 Fzr/Cdh1 Promotes the Differentiation of Neural Stem Cell Lineages in Drosophila Ly, Phuong Thao Wang, Hongyan Front Cell Dev Biol Cell and Developmental Biology How stem cells and progenitors balance between self-renewal and differentiation is a central issue of stem cell biology. Here, we describe a novel and essential function of Drosophila Fzr/Cdh1, an evolutionary conserved protein, during the differentiation of neural stem cell (NSC) lineages in the central nervous system. We show that Fzr, a known co-activator of Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase, promotes the production of neurons from neural progenitors called ganglion mother cells (GMCs). However, knockdown of APC/C subunit Ida or another APC/C co-activator CDC20 does not similarly impair GMC-neuron transition. We also observe a concomitant loss of differentiation factor Prospero expression and ectopic accumulation of mitotic kinase Polo in fzr mutant clones, strongly supporting the impairment of GMC to neuron differentiation. Besides functioning in GMCs, Fzr is also present in NSCs to facilitate the production of intermediate neural progenitors from NSCs. Taken together, Fzr plays a novel function in promoting differentiation programs during Drosophila NSC lineage development. Given that human Fzr is inactivated in multiple types of human cancers including brain tumors and that Fzr regulates neurotoxicity in various models of neurodegenerative diseases, our study on the role of Fzr in turning off proliferation in neuronal cells may provide insights into how Fzr deficits may contribute to human neurodegenerative diseases and tumors. Frontiers Media S.A. 2020-02-11 /pmc/articles/PMC7026481/ /pubmed/32117986 http://dx.doi.org/10.3389/fcell.2020.00060 Text en Copyright © 2020 Ly and Wang. http://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
Ly, Phuong Thao
Wang, Hongyan
Fzr/Cdh1 Promotes the Differentiation of Neural Stem Cell Lineages in Drosophila
title Fzr/Cdh1 Promotes the Differentiation of Neural Stem Cell Lineages in Drosophila
title_full Fzr/Cdh1 Promotes the Differentiation of Neural Stem Cell Lineages in Drosophila
title_fullStr Fzr/Cdh1 Promotes the Differentiation of Neural Stem Cell Lineages in Drosophila
title_full_unstemmed Fzr/Cdh1 Promotes the Differentiation of Neural Stem Cell Lineages in Drosophila
title_short Fzr/Cdh1 Promotes the Differentiation of Neural Stem Cell Lineages in Drosophila
title_sort fzr/cdh1 promotes the differentiation of neural stem cell lineages in drosophila
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026481/
https://www.ncbi.nlm.nih.gov/pubmed/32117986
http://dx.doi.org/10.3389/fcell.2020.00060
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