Biosynthesis of Wdr16, a marker protein for kinocilia-bearing cells, starts at the time of kinocilia formation in rat, and wdr16 gene knockdown causes hydrocephalus in zebrafish.
The rat ortholog of the WD40 repeat protein Wdr16 is abundantly expressed in testis and cultured ependymal cells. Low levels are found in lung and brain, respectively, while it is absent from kinocilia-free tissues. In testis and ependymal primary cultures, Wdr16 messenger RNA appears concomitantly with the messages for sperm-associated antigen 6, a kinocilia marker, and for hydin, a protein linked to ciliary function and hydrocephalus. In testis, ependyma and respiratory epithelium, the Wdr16 protein is up-regulated together with kinocilia formation. The wdr16 gene is restricted to genera in possession of kinocilia, and it is strongly conserved during evolution. The human and zebrafish proteins are identical in 62% of their aligned amino acids. On the message level, the zebrafish Wdr16 ortholog was found exclusively in kinocilia-bearing tissues by in situ hybridisation. Gene knockdown in zebrafish embryos by antisense morpholino injection resulted in severe hydrocephalus formation with unaltered ependymal morphology or ciliary beat. Wdr16 can be considered a differentiation marker of kinocilia-bearing cells. In the brain, it appears to be functionally related to water homeostasis or osmoregulation.
Hirschner
Wolfgang
W
Interfaculty Institute for Biochemistry, University of Tuebingen, Tuebingen, Germany.
Pogoda
Hans-Martin
HM
Kramer
Carina
C
Thiess
Ulrike
U
Hamprecht
Bernd
B
Wiesmüller
Karl-Heinz
KH
Lautner
Matthias
M
Verleysdonk
Stephan
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism*; D002925:Ciliary Motility Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004805:Ependyma / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D006849:Hydrocephalus / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020547:Lateral Ventricles / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014882:Water-Electrolyte Balance / Q000235:genetics / Q000502:physiology; D015027:Zebrafish / Q000002:abnormalities*; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification
D015415:Biomarkers; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D029961:Zebrafish Proteins; C519769:cfap52 protein, zebrafish