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

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 vertebratespecific 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.

Trunk neural crest cells: formation, migration and beyond

“…Although the head-trunk differentiation in the lamprey is not yet completed and there is no clear differentiation in trunk and cranial NC in this species, BC cells can be considered similar to tNC since the branchial region is expanded caudally. In regard to their migration, BC cells are found superficially to the arch mesoderm, indicating that these cells migrate along the dorsolateral pathway (Mukendi et al, 2016). All the results mentioned above stress the fact that migration of NCCs varies between different species and among various phyla.…”

11-Deoxycortisol controls hydromineral balance in the most basal osmoregulating vertebrate, sea lamprey (Petromyzon marinus)

“…It is known that tight junction (TJ) complexes dynamically control paracellular permeability in many vertebrate epithelia, including changes in gill epithelium of teleost fishes from "tight" in FW to "leaky" in SW 35 . A functional role for TJ complex proteins has more recently been elucidated in the sea lamprey [35][36][37][38] . Several studies have demonstrated putative corticosteroid control of TJ proteins in cultured teleost fish gill epithelia 24,39,40 , and it is possible that S may thus also control TJ complexing and paracellular permeability in the sea lamprey gill, in addition to its role in controlling active ion transport.…”

Claudins of sea lamprey (Petromyzon marinus) – organ‐specific expression and transcriptional responses to water of varying ion content

“…Architectural heterogeneity and plasticity of lamprey TJs have been acknowledged for some time; nonetheless, the molecular components of the TJ complex in this group of ancient, jawless vertebrates are poorly understood (Kolosov et al ., ; Mukendi et al ., ). The transcriptional dynamics of genes encoding Cldn TJ proteins in pre‐ and post‐metamorphic sea lampreys, especially in osmoregulatory organs following changes in environmental ion levels, consolidate the ability to accept the hypothesis that the molecular physiology of the sea lamprey TJ complex plays an important role in sea lamprey osmoregulation.…”

“…It is, however, clear that the expansion of the Cldn superfamily of TJ proteins evident in jawed fishes did not occur until after their split from agnathans, leaving the latter to cope with the same osmoregulatory burden as jawed fishes but with a much smaller TJ protein complement. A recent study identified 18 sea lamprey cldns and profiled their expression during the embryonic development of ammocoetes (Mukendi et al ., ). The current study, in contrast, focused on the role of select cldns in acclimation strategies of ammocoetes to an ion‐poor environment and post‐metamorphic lampreys to hyperosmotic conditions.…”

“…In addition, Cldn‐18 knockout mice developed alveolar lung barrier dysfunction (Lafemina et al ., ). Previously, cldn‐18 was reported to be expressed in non‐neural ectoderm and pharyngeal arches of developing sea lamprey embryos (Mukendi et al ., ). This suggests that Cldn‐18 may be a barrier‐forming TJ protein in the sea lamprey, important for the protection of the SW‐acclimated sea lamprey from intestinal salt loading and ion retention in the kidney of ammocoete.…”