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...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2020
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| Online Access: | https://hdl.handle.net/10356/145151 |
| _version_ | 1811685188761026560 |
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| author | Ly, Phuong Thao Wang, Hongyan |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Ly, Phuong Thao Wang, Hongyan |
| author_sort | Ly, Phuong Thao |
| collection | NTU |
| 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. |
| first_indexed | 2024-10-01T04:40:33Z |
| format | Journal Article |
| id | ntu-10356/145151 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:40:33Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1451512023-02-28T17:05:52Z Fzr/Cdh1 promotes the differentiation of neural stem cell lineages in Drosophila Ly, Phuong Thao Wang, Hongyan School of Biological Sciences Science::Biological sciences NSC Neuroblast 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. Ministry of Education (MOE) Ministry of Health (MOH) Published version This work was supported by Duke-NUS Signature Research Program funded by Ministry of Health and Ministry of Education tier 2 (MOE2017-T2-2-025) to HW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 2020-12-14T06:27:25Z 2020-12-14T06:27:25Z 2020 Journal Article Ly, P. T., & Wang, H. (2020). Fzr/Cdh1 promotes the differentiation of neural stem cell lineages in Drosophila. Frontiers in Cell and Developmental Biology, 8, 60-. doi:10.3389/fcell.2020.00060 2296-634X https://hdl.handle.net/10356/145151 10.3389/fcell.2020.00060 32117986 8 en MOE2017-T2-2-025 Frontiers in Cell and Developmental Biology © 2020 Ly and Wang. 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. application/pdf |
| spellingShingle | Science::Biological sciences NSC Neuroblast 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 | Science::Biological sciences NSC Neuroblast |
| url | https://hdl.handle.net/10356/145151 |
| work_keys_str_mv | AT lyphuongthao fzrcdh1promotesthedifferentiationofneuralstemcelllineagesindrosophila AT wanghongyan fzrcdh1promotesthedifferentiationofneuralstemcelllineagesindrosophila |