PUBLICATION
ppargc1a controls nephron segmentation during zebrafish embryonic kidney ontogeny
- Authors
- Chambers, J.M., Poureetezadi, S.J., Addiego, A., Lahne, M., Wingert, R.A.
- ID
- ZDB-PUB-181127-81
- Date
- 2018
- Source
- eLIFE 7: (Journal)
- Registered Authors
- Chambers, Joseph, Poureetezadi, Shahram, Wingert, Rebecca
- Keywords
- developmental biology, zebrafish
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Bezafibrate/pharmacology
- Body Patterning*/drug effects
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Gene Expression Regulation, Developmental/drug effects
- Genetic Testing
- Morpholinos/pharmacology
- Nephrons/drug effects
- Nephrons/embryology*
- Nephrons/metabolism
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/chemistry
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*
- Phenotype
- Pronephros/drug effects
- Pronephros/embryology
- Pronephros/metabolism
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Signal Transduction/drug effects
- Small Molecule Libraries/pharmacology
- Transcription Factors/metabolism
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 30475208 Full text @ Elife
Citation
Chambers, J.M., Poureetezadi, S.J., Addiego, A., Lahne, M., Wingert, R.A. (2018) ppargc1a controls nephron segmentation during zebrafish embryonic kidney ontogeny. eLIFE. 7:.
Abstract
Nephron segmentation involves a concert of genetic and molecular signals that are not fully understood. Through a chemical screen, we discovered that alteration of peroxisome proliferator-activated receptor (PPAR) signaling disrupts nephron segmentation in the zebrafish embryonic kidney (Poureetezadi et al., 2016). Here, we show that the PPAR co-activator ppargc1a directs renal progenitor fate. ppargc1a mutants form a small distal late (DL) segment and an expanded proximal straight tubule (PST) segment. ppargc1a promotes DL fate by regulating the transcription factor tbx2b, and restricts expression of the transcription factor sim1a to inhibit PST fate. Interestingly, sim1a restricts ppargc1a expression to promote the PST, and PST development is fully restored in ppargc1a/sim1a deficient embryos, suggesting Ppargc1a and Sim1a counterbalance each other in an antagonistic fashion to delineate the PST segment boundary during nephrogenesis. Taken together, our data reveal new roles for Ppargc1a during development, which have implications for understanding renal birth defects.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping