The transcription factors Tfeb and Tfe3 are required for survival and embryonic development of pancreas and liver in zebrafish.
The transcription factors TFEB and TFE3 modulate expression of lysosomal, autophagic, and metabolic genes to restore energy and cellular homeostasis in response to a variety of stress conditions. Since their role during vertebrate development is less characterized, we used CRISPR/Cas9 to deplete tfe...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-06-01
|
| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1011754 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849427952560766976 |
|---|---|
| author | Alberto Rissone Martina La Spina Erica Bresciani Zulfeqhar A Syed Christian A Combs Martha Kirby Abdel Elkahloun Vicky Chen Raman Sood Shawn M Burgess Rosa Puertollano |
| author_facet | Alberto Rissone Martina La Spina Erica Bresciani Zulfeqhar A Syed Christian A Combs Martha Kirby Abdel Elkahloun Vicky Chen Raman Sood Shawn M Burgess Rosa Puertollano |
| author_sort | Alberto Rissone |
| collection | DOAJ |
| description | The transcription factors TFEB and TFE3 modulate expression of lysosomal, autophagic, and metabolic genes to restore energy and cellular homeostasis in response to a variety of stress conditions. Since their role during vertebrate development is less characterized, we used CRISPR/Cas9 to deplete tfeb, tfe3a, and tfe3b in zebrafish. The simultaneous lack of these genes compromised embryo survival during early development, with an almost complete lethality of the larvae by 8-10 dpf. The knockout animals showed apoptosis in brain and retina and alterations in pancreas, liver, and gut. Exocrine pancreas presented the most severe defects, with accumulation of abnormal zymogen granules leading to acinar atrophy in embryos and pancreatitis-like phenotypes in adults; likely due to a block of the autophagy machinery implicated in removal of damaged granules. Knockout animals displayed increased susceptibility to oxidative and heat-shock stress. Our work reveals an essential role of Tfeb and Tfe3 in maintaining cellular and tissue homeostasis during development. |
| format | Article |
| id | doaj-art-8fb95e79e6444f94beffa09e11582853 |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-8fb95e79e6444f94beffa09e115828532025-08-20T03:28:51ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042025-06-01216e101175410.1371/journal.pgen.1011754The transcription factors Tfeb and Tfe3 are required for survival and embryonic development of pancreas and liver in zebrafish.Alberto RissoneMartina La SpinaErica BrescianiZulfeqhar A SyedChristian A CombsMartha KirbyAbdel ElkahlounVicky ChenRaman SoodShawn M BurgessRosa PuertollanoThe transcription factors TFEB and TFE3 modulate expression of lysosomal, autophagic, and metabolic genes to restore energy and cellular homeostasis in response to a variety of stress conditions. Since their role during vertebrate development is less characterized, we used CRISPR/Cas9 to deplete tfeb, tfe3a, and tfe3b in zebrafish. The simultaneous lack of these genes compromised embryo survival during early development, with an almost complete lethality of the larvae by 8-10 dpf. The knockout animals showed apoptosis in brain and retina and alterations in pancreas, liver, and gut. Exocrine pancreas presented the most severe defects, with accumulation of abnormal zymogen granules leading to acinar atrophy in embryos and pancreatitis-like phenotypes in adults; likely due to a block of the autophagy machinery implicated in removal of damaged granules. Knockout animals displayed increased susceptibility to oxidative and heat-shock stress. Our work reveals an essential role of Tfeb and Tfe3 in maintaining cellular and tissue homeostasis during development.https://doi.org/10.1371/journal.pgen.1011754 |
| spellingShingle | Alberto Rissone Martina La Spina Erica Bresciani Zulfeqhar A Syed Christian A Combs Martha Kirby Abdel Elkahloun Vicky Chen Raman Sood Shawn M Burgess Rosa Puertollano The transcription factors Tfeb and Tfe3 are required for survival and embryonic development of pancreas and liver in zebrafish. PLoS Genetics |
| title | The transcription factors Tfeb and Tfe3 are required for survival and embryonic development of pancreas and liver in zebrafish. |
| title_full | The transcription factors Tfeb and Tfe3 are required for survival and embryonic development of pancreas and liver in zebrafish. |
| title_fullStr | The transcription factors Tfeb and Tfe3 are required for survival and embryonic development of pancreas and liver in zebrafish. |
| title_full_unstemmed | The transcription factors Tfeb and Tfe3 are required for survival and embryonic development of pancreas and liver in zebrafish. |
| title_short | The transcription factors Tfeb and Tfe3 are required for survival and embryonic development of pancreas and liver in zebrafish. |
| title_sort | transcription factors tfeb and tfe3 are required for survival and embryonic development of pancreas and liver in zebrafish |
| url | https://doi.org/10.1371/journal.pgen.1011754 |
| work_keys_str_mv | AT albertorissone thetranscriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT martinalaspina thetranscriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT ericabresciani thetranscriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT zulfeqharasyed thetranscriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT christianacombs thetranscriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT marthakirby thetranscriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT abdelelkahloun thetranscriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT vickychen thetranscriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT ramansood thetranscriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT shawnmburgess thetranscriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT rosapuertollano thetranscriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT albertorissone transcriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT martinalaspina transcriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT ericabresciani transcriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT zulfeqharasyed transcriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT christianacombs transcriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT marthakirby transcriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT abdelelkahloun transcriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT vickychen transcriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT ramansood transcriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT shawnmburgess transcriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish AT rosapuertollano transcriptionfactorstfebandtfe3arerequiredforsurvivalandembryonicdevelopmentofpancreasandliverinzebrafish |