Int. J. Dev. Biol. 60: 39 - 51 (2016)
doi: 10.1387/ijdb.150364nn
© UPV/EHU Press

Evolution of the vertebrate claudin gene family: insights from a basal vertebrate, the sea lamprey

Christian Mukendi1, Nicholas Dean1, Rushil Lala1, Jeramiah Smith2, Marianne E. Bronner3 and Natalya V. Nikitina*,1

1School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa, 2Department of Biology, University of Kentucky, Lexington, KY, USA and 3Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA

ABSTRACT Claudins are major constituents of tight junctions, contributing both to their intercellular sealing and selective permeability properties. While claudins and claudin-like molecules are present in some invertebrates, the association of claudins with tight junctions has been conclusively documented only in vertebrates. Here we report the sequencing, phylogenetic analysis and comprehensive spatiotemporal expression analysis of the entire claudin gene family in the basal extant vertebrate, the sea lamprey. Our results demonstrate that clear orthologues to about half of all mammalian claudins are present in the lamprey, suggesting that at least one round of whole genome duplication contributed to the diversification of this gene family. Expression analysis revealed that claudins are expressed in discrete and specific domains, many of which represent vertebrate-specific innovations, such as in cranial ectodermal placodes and the neural crest; whereas others represent structures characteristic of chordates, e.g. pronephros, notochord, somites, endostyle and pharyngeal arches. By comparing the embryonic expression of claudins in the lamprey to that of other vertebrates, we found that ancestral expression patterns were often preserved in higher vertebrates. Morpholino mediated loss of Cldn3b demonstrated a functional role for this protein in placode and pharyngeal arch morphogenesis. Taken together, our data provide novel insights into the origins and evolution of the claudin gene family and the significance of claudin proteins in the evolution of vertebrates.

Keywords:

claudin, lamprey, vertebrate primordia, embryo

*Corresponding author e-mail: natalya.nikitina@wits.ac.za