The Batten disease gene Cln3 is required for the activation of intestinal stem cell during regeneration via JAK/STAT signaling in Drosophila
CLN3 mutation causes Juvenile neuronal ceroid lipofuscinosis (JNCL, also known as Batten disease), an early onset neurodegenerative disorder. Patients who suffer from Batten disease often die at an early age. However, the mechanisms underlying how CLN3 loss develops Batten disease remain largely unc...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1508714/full |
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| author | Zihua Yu Zihua Yu Jinhua Yan Zhiming Liu Haiyan Wang Guanzheng Luo Haiyang Chen |
| author_facet | Zihua Yu Zihua Yu Jinhua Yan Zhiming Liu Haiyan Wang Guanzheng Luo Haiyang Chen |
| author_sort | Zihua Yu |
| collection | DOAJ |
| description | CLN3 mutation causes Juvenile neuronal ceroid lipofuscinosis (JNCL, also known as Batten disease), an early onset neurodegenerative disorder. Patients who suffer from Batten disease often die at an early age. However, the mechanisms underlying how CLN3 loss develops Batten disease remain largely unclear. Here, using Drosophila midgut system, we demonstrate that Drosophila Cln3 has no effect on midgut homeostasis maintaince, including cellular component, intestinal stem cells (ISCs) proliferation and differentiation, but is necessary for ISC activation upon tissue damage. Cell type-specific Gal4 screening reveals that the failure of ISC activation during regeneration caused by Cln3 loss is ISC-autonomous. Through genetic analyses, we elucidate that JAK/STAT signaling in ISCs is not activated with Cln3 depletion upon tissue damage, and functions downstream of Cln3. Our study provides a potential mechanism underlying the development of CLN3-mediated Batten disease at cellular level. |
| format | Article |
| id | doaj-art-30019e241761449c934b7b6f9859389d |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-30019e241761449c934b7b6f9859389d2025-01-23T06:56:25ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-01-011310.3389/fcell.2025.15087141508714The Batten disease gene Cln3 is required for the activation of intestinal stem cell during regeneration via JAK/STAT signaling in DrosophilaZihua Yu0Zihua Yu1Jinhua Yan2Zhiming Liu3Haiyan Wang4Guanzheng Luo5Haiyang Chen6MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaWest China Centre of Excellence for Pancreatitis and Laboratory of Stem Cell and Anti-Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaWest China Centre of Excellence for Pancreatitis and Laboratory of Stem Cell and Anti-Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaWest China Centre of Excellence for Pancreatitis and Laboratory of Stem Cell and Anti-Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaWest China Centre of Excellence for Pancreatitis and Laboratory of Stem Cell and Anti-Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaMOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaWest China Centre of Excellence for Pancreatitis and Laboratory of Stem Cell and Anti-Aging Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaCLN3 mutation causes Juvenile neuronal ceroid lipofuscinosis (JNCL, also known as Batten disease), an early onset neurodegenerative disorder. Patients who suffer from Batten disease often die at an early age. However, the mechanisms underlying how CLN3 loss develops Batten disease remain largely unclear. Here, using Drosophila midgut system, we demonstrate that Drosophila Cln3 has no effect on midgut homeostasis maintaince, including cellular component, intestinal stem cells (ISCs) proliferation and differentiation, but is necessary for ISC activation upon tissue damage. Cell type-specific Gal4 screening reveals that the failure of ISC activation during regeneration caused by Cln3 loss is ISC-autonomous. Through genetic analyses, we elucidate that JAK/STAT signaling in ISCs is not activated with Cln3 depletion upon tissue damage, and functions downstream of Cln3. Our study provides a potential mechanism underlying the development of CLN3-mediated Batten disease at cellular level.https://www.frontiersin.org/articles/10.3389/fcell.2025.1508714/fullDrosophilaintestinal stem cell (ISC)Batten diseaseCLN3JAK/STAT signaling pathway |
| spellingShingle | Zihua Yu Zihua Yu Jinhua Yan Zhiming Liu Haiyan Wang Guanzheng Luo Haiyang Chen The Batten disease gene Cln3 is required for the activation of intestinal stem cell during regeneration via JAK/STAT signaling in Drosophila Frontiers in Cell and Developmental Biology Drosophila intestinal stem cell (ISC) Batten disease CLN3 JAK/STAT signaling pathway |
| title | The Batten disease gene Cln3 is required for the activation of intestinal stem cell during regeneration via JAK/STAT signaling in Drosophila |
| title_full | The Batten disease gene Cln3 is required for the activation of intestinal stem cell during regeneration via JAK/STAT signaling in Drosophila |
| title_fullStr | The Batten disease gene Cln3 is required for the activation of intestinal stem cell during regeneration via JAK/STAT signaling in Drosophila |
| title_full_unstemmed | The Batten disease gene Cln3 is required for the activation of intestinal stem cell during regeneration via JAK/STAT signaling in Drosophila |
| title_short | The Batten disease gene Cln3 is required for the activation of intestinal stem cell during regeneration via JAK/STAT signaling in Drosophila |
| title_sort | batten disease gene cln3 is required for the activation of intestinal stem cell during regeneration via jak stat signaling in drosophila |
| topic | Drosophila intestinal stem cell (ISC) Batten disease CLN3 JAK/STAT signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1508714/full |
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