Nephrocystin-3 is required for ciliary function in zebrafish embryos

Weibin Zhou, Julie Dai, Massimo Attanasio, Friedhelm Hildebrandt

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Nephronophthisis (NPHP) is the most frequent genetic cause of end-stage renal failure in the first three decades of life. It is characterized primarily by renal cysts with extrarenal involvements of the eye and brain. Ten recessive genes responsible for NPHP have been identified by positional cloning. This discovery supported a unifying theory of renal cystic disease, which states that all proteins mutated in cystic kidney diseases of human, mice, or zebrafish are expressed in primary cilia of renal epithelial cells. Mutations in nephrocystin-3 (NPHP3) are the cause of human nephronophthisis type 3 and polycystic kidney disease (pcy) mouse mutants. To study the functional role of NPHP3 in normal embryonic development and in the pathogenesis of cystic kidney disease, we characterized the zebrafish ortholog nphp3 by morpholino oligo (MO)-mediated knockdown. When nphp3 function was suppressed by either of the two MOs blocking the translation of the protein or the splicing of mRNA, zebrafish embryos displayed hydrocephalus and pronephric cysts. Knockdown of nphp3 also led to situs inversus phenotypes due to defective cilia at Kupffer's vesicle. We showed that nphp3 genetically interacts with nphp2/inversin and human NPHP3 localizes to primary cilia in Madin-Darby canine kidney cells. Like nphp2/inversin, nphp3 knockdown affected morphogenic cell movement during gastrulation, suggesting nphp3 is essential to regulate convergent extension. Thus nphp3, cooperating with nphp2/inversin, plays an essential role related to ciliary function, and the knockdown provides an animal model that may be used for studies of the pathogenesis and therapy for this disease.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume299
Issue number1
DOIs
StatePublished - Jul 2010

Fingerprint

Cystic Kidney Diseases
Cilia
Zebrafish
Embryonic Structures
Cysts
Protein Splicing
Situs Inversus
Kidney
Recessive Genes
Morpholinos
Polycystic Kidney Diseases
Gastrulation
Madin Darby Canine Kidney Cells
Hydrocephalus
Chronic Kidney Failure
Embryonic Development
Cell Movement
Organism Cloning
Animal Models
Epithelial Cells

Keywords

  • Cilium
  • Kidney cyst
  • Kupffer's vesicle
  • Nephronophthisis
  • Situs inversus

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Nephrocystin-3 is required for ciliary function in zebrafish embryos. / Zhou, Weibin; Dai, Julie; Attanasio, Massimo; Hildebrandt, Friedhelm.

In: American Journal of Physiology - Renal Physiology, Vol. 299, No. 1, 07.2010.

Research output: Contribution to journalArticle

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