Tjp3/zo-3 is critical for epidermal barrier function in zebrafish embryos.
TJP3/ZO-3 is a scaffolding protein that tethers tight junction integral membrane proteins to the actin cytoskeleton and links the conserved Crumbs polarity complex to tight junctions. The physiological function of TJP3/ZO-3 is not known and mice lacking TJP3/ZO-3 show no apparent phenotype. Here we show that Tjp3/Zo-3 is a component of tight junctions present in the enveloping cell layer of zebrafish embryos. Silencing tjp3/zo-3 using morpholinos leads to edema, loss of blood circulation and tail fin malformations in the embryos. The ultrastructure of tight junctions of the enveloping cell layer is disrupted, without affecting the asymmetric distribution of plasma membrane proteins. Morphants show a loss of the epidermal barrier, as assessed by an increased permeability of the enveloping cell layer to low molecular weight tracers and a higher sensitivity of the embryos to osmotic stress. Subjecting wild-type embryos to osmotic stress mimicks the morphant phenotype, consistent with the phenotype being a direct consequence of failed osmoregulation. Thus, Tjp3/Zo-3 is critical for barrier function of the enveloping cell layer and osmoregulation in early stages of zebrafish development.
Kiener
Tanja K
TK
Epithelial Cell Biology Laboratory, Institute of Molecular and Cell Biology, A*STAR (Agency for Science Technology and Research), Singapore 138673, Singapore.
Selptsova-Friedrich
Inna
I
Hunziker
Walter
W
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics; D004817:Epidermis / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009997:Osmotic Pressure / Q000187:drug effects; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D062825:Zonula Occludens Proteins
D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D029961:Zebrafish Proteins; D062825:Zonula Occludens Proteins; C524047:tjp3 protein, zebrafish