PUBLICATION
Nephrocystin-4 is required for pronephric duct-dependent cloaca formation in zebrafish
- Authors
- Slanchev, K., Pütz, M., Schmitt, A., Kramer-Zucker, A., and Walz, G.
- ID
- ZDB-PUB-110602-26
- Date
- 2011
- Source
- Human molecular genetics 20(16): 3119-28 (Journal)
- Registered Authors
- Kramer-Zucker, Albrecht, Slanchev, Krasimir
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Cell Movement
- Cilia/metabolism
- Cloaca/embryology*
- Cloaca/metabolism
- Cloaca/pathology
- Cloning, Molecular
- Embryo, Nonmammalian/metabolism
- Embryo, Nonmammalian/pathology
- Gene Expression Regulation, Developmental
- Gene Knockdown Techniques
- Molecular Sequence Data
- Nephrons/embryology*
- Nephrons/metabolism
- Nephrons/pathology
- Phenotype
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 21596840 Full text @ Hum. Mol. Genet.
Citation
Slanchev, K., Pütz, M., Schmitt, A., Kramer-Zucker, A., and Walz, G. (2011) Nephrocystin-4 is required for pronephric duct-dependent cloaca formation in zebrafish. Human molecular genetics. 20(16):3119-28.
Abstract
NPHP4 mutations cause nephronophthisis, an autosomal recessive cystic kidney disease associated with renal fibrosis and kidney failure. The NPHP4 gene product nephrocystin-4 interacts with other nephrocystins, cytoskeletal and ciliary proteins; however, the molecular and cellular functions of nephrocystin-4 have remained elusive. Here we demonstrate that nephrocystin-4 is required for normal cloaca formation during zebrafish embryogenesis. Time-lapse imaging of the developing zebrafish pronephros revealed that tubular epithelial cells at the distal pronephros actively migrate between the yolk sac extension and the blood island towards the ventral fin fold to join the proctodeum and to form the cloaca. Nphp4-deficient pronephric duct cells failed to connect with their ectodermal counterparts, and instead formed a vesicle at the obstructed end of the pronephric duct. Nephrocystin-4 interacts with nephrocystin-1 and Par6. Depletion of zebrafish NPHP1 (nphp1) increased the incidence of cyst formation and randomization of the normal body axis, but did not augment cloaca malformation in nphp4-deficient zebrafish embryos. However, simultaneous depletion of zebrafish Par6 (pard6) aggravated cloaca formation defects in nphp4-depleted embryos, suggesting that nphp4 orchestrates directed cell migration and cloaca formation through interaction with the Par protein complex.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping