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Nephrocystin-4 is required for pronephric duct-dependent cloaca formation in zebrafish.
- Source :
-
Human molecular genetics [Hum Mol Genet] 2011 Aug 15; Vol. 20 (16), pp. 3119-28. Date of Electronic Publication: 2011 May 19. - Publication Year :
- 2011
-
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.
- Subjects :
- Amino Acid Sequence
Animals
Cell Movement
Cilia metabolism
Cloaca metabolism
Cloaca pathology
Cloning, Molecular
Embryo, Nonmammalian metabolism
Embryo, Nonmammalian pathology
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Molecular Sequence Data
Nephrons metabolism
Nephrons pathology
Phenotype
Zebrafish genetics
Zebrafish Proteins chemistry
Zebrafish Proteins deficiency
Zebrafish Proteins genetics
Cloaca embryology
Nephrons embryology
Zebrafish embryology
Zebrafish Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2083
- Volume :
- 20
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Human molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 21596840
- Full Text :
- https://doi.org/10.1093/hmg/ddr214