PUBLICATION
The transcription factors Tfeb and Tfe3 are required for survival and embryonic development of pancreas and liver in zebrafish
- Authors
- Rissone, A., La Spina, M., Bresciani, E., Syed, Z.A., Combs, C.A., Kirby, M., Elkahloun, A., Chen, V., Sood, R., Burgess, S.M., Puertollano, R.
- ID
- ZDB-PUB-250628-9
- Date
- 2025
- Source
- PLoS Genetics 21: e1011754e1011754 (Journal)
- Registered Authors
- Bresciani, Erica, Puertollano, Rosa, Sood, Raman
- Keywords
- none
- Datasets
- GEO:GSE278733
- MeSH Terms
-
- Gene Expression Regulation, Developmental
- Oxidative Stress/genetics
- Autophagy/genetics
- CRISPR-Cas Systems
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/growth & development
- Liver*/embryology
- Liver*/growth & development
- Liver*/metabolism
- Embryonic Development*/genetics
- Pancreas*/embryology
- Pancreas*/growth & development
- Pancreas*/metabolism
- Apoptosis/genetics
- Animals
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors*/genetics
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors*/metabolism
- PubMed
- 40577485 Full text @ PLoS Genet.
Citation
Rissone, A., La Spina, M., Bresciani, E., Syed, Z.A., Combs, C.A., Kirby, M., Elkahloun, A., Chen, V., Sood, R., Burgess, S.M., Puertollano, R. (2025) The transcription factors Tfeb and Tfe3 are required for survival and embryonic development of pancreas and liver in zebrafish. PLoS Genetics. 21:e1011754e1011754.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping