Nephrocystin-4 is required for pronephric duct-dependent cloaca formation in zebrafish
| Autor: | Gerd Walz, Krasimir Slanchev, Annette Schmitt, Albrecht Kramer-Zucker, Michael Pütz |
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| Rok vydání: | 2011 |
| Předmět: |
Embryo
Nonmammalian animal structures Molecular Sequence Data Pronephric duct Cystic kidney disease Cloaca Cell Movement Nephronophthisis Genetics medicine Animals Amino Acid Sequence Cilia Cloning Molecular Yolk sac Molecular Biology Zebrafish Genetics (clinical) biology Gene Expression Regulation Developmental Nephrons General Medicine Anatomy Zebrafish Proteins biology.organism_classification medicine.disease Pronephros Cell biology Phenotype medicine.anatomical_structure Cloaca (embryology) Gene Knockdown Techniques embryonic structures Proctodeum |
| Zdroj: | Human Molecular Genetics. 20:3119-3128 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddr214 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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