Overexpression of the Xenopus tight-junction protein claudin causes randomization of the left-right body axis

This study presents Xenopus claudin (Xcla), a tight-junction protein that i s abundantly expressed in eggs and neuroectodermal precursors during early development. It was isolated via a differential screen for mRNAs enriched i n microsomes in the Xenopus blastula. The Xcla protein contains four transm embrane domains and a carboxy-terminal cytoplasmic region with a putative P DZ-binding site. We show that this PDZ-binding site of Xcla is critical for its correct localization on the cell membrane and that a truncated form le ads to delocalization of the tight-junction protein ZO-1. Overexpression of Xcla causes changes in the cell adhesion properties of blastomeres and lea ds to visceral situs randomization. The results suggest that left-right axi al patterning is very sensitive to changes in regulation of cell-cell inter actions and implicate a tight-junction protein in the determination of left -right asymmetry. (C) 2001 Academic Press.