PUBLICATION
Neph3 associates with regulation of glomerular and neural development in zebrafish
- Authors
- Wang, H., Lehtonen, S., Chen, Y.C., Heikkilä, E., Panula, P., and Holthöfer, H.
- ID
- ZDB-PUB-111122-36
- Date
- 2012
- Source
- Differentiation; research in biological diversity 83(1): 38-46 (Journal)
- Registered Authors
- Panula, Pertti
- Keywords
- kidney development, glomerulus, podocyte, Neph3, kirrel2, zebrafish
- MeSH Terms
-
- Animals
- Brain/anatomy & histology
- Brain/embryology
- Gene Expression Regulation, Developmental
- Intracellular Signaling Peptides and Proteins/genetics
- Intracellular Signaling Peptides and Proteins/metabolism
- Kidney Glomerulus/anatomy & histology
- Kidney Glomerulus/embryology*
- Kidney Glomerulus/metabolism
- Membrane Proteins/genetics*
- Membrane Proteins/metabolism
- Nephrons/embryology*
- Nephrons/growth & development
- Neurogenesis/genetics
- Oligodeoxyribonucleotides, Antisense/genetics
- Podocytes/metabolism
- Pronephros/embryology
- Pronephros/growth & development
- RNA, Messenger/genetics
- Zebrafish/embryology*
- Zebrafish/genetics*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 22099175 Full text @ Differentiation
Citation
Wang, H., Lehtonen, S., Chen, Y.C., Heikkilä, E., Panula, P., and Holthöfer, H. (2012) Neph3 associates with regulation of glomerular and neural development in zebrafish. Differentiation; research in biological diversity. 83(1):38-46.
Abstract
Neph3 (filtrin) is a membrane protein expressed in the glomerular epithelial cells (podocytes), but its role in the glomerulus is still largely unknown. To characterize the function of Neph3 in the glomerulus, we employed the zebrafish as a model system. Here we show that the expression of neph3 in pronephros starts before the onset of nephrin and podocin expression, peaks when the nephron primordium differentiates into glomerulus and tubulus, and is then downregulated upon glomerular maturation. By histology, we found that neph3 is specifically expressed in pronephric podocytes at 36 hpf. Furthermore, disruption of neph3 expression by antisense morpholino oligonucleotides results in distorted body curvature and transient pericardial edema, the latter likely reflecting perturbation of glomerular osmoregulatory function. Histological analysis of neph3 morphants reveals altered glomerular morphology and dilated pronephric tubules. The phenotype of neph3 morphants, curved body and pericardial edema, is rescued by wild-type zebrafish neph3 mRNA. In addition to glomerulus, neph3 is highly expressed in the developing brain and specific regions of mature midbrain and hindbrain. In line with this, neph3 morphants show aberrant brain morphology. Collectively, the expression of neph3 in glomerulus and brain together with the morphant phenotype imply that neph3 is a pleiotropic gene active during distinct stages of tissue differentiation and associates directly in the regulation of both glomerular and neural development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping