A Novel Role for VICKZ Proteins in Maintaining Epithelial Integrity during Embryogenesis

• Published in: PloS one 2015-08, Vol.10 (8), p.e0136408-e0136408
• Main Authors: Carmel, Michal Shoshkes, Kahane, Nitza, Oberman, Froma, Miloslavski, Rachel, Sela-Donenfeld, Dalit, Kalcheim, Chaya, Yisraeli, Joel K
• Format: Article
• Language: English
• Subjects: Animals; Avian Proteins - genetics; Avian Proteins - metabolism; Binding proteins; Binding sites; Cancer; Cell adhesion & migration; Cell migration; Cell Movement - physiology; Chick Embryo; Developmental biology; Down-regulation; Electroporation; Embryo fibroblasts; Embryogenesis; Embryonic development; Embryonic Development - physiology; Embryonic growth stage; Embryos; Emigration; Epithelial-Mesenchymal Transition - physiology; Epithelium; Epithelium - embryology; Fibroblasts; Fibroblasts - cytology; Fibroblasts - metabolism; Genetic aspects; Integrity; Laminin; Localization; Medical prognosis; Medical research; Medicine; Mesencephalon; Mesenchyme; mRNA; Neural crest; Neural tube; Neurobiology; Neurosciences; Numerical controls; Physiological aspects; Proteins; Ribonucleic acid; RNA; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Singers; Transplantation; Xenopus; Xenopus laevis; Xenopus Proteins - genetics; Xenopus Proteins - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0136408

VICKZ (IGF2BP1,2,3/ZBP1/Vg1RBP/IMP1,2,3) proteins bind RNA and help regulate many RNA-mediated processes. In the midbrain region of early chick embryos, VICKZ is expressed in the neural folds and along the basal surface of the neural epithelium, but, upon neural tube closure, is down-regulated in prospective cranial neural crest (CNC) cells, concomitant with their emigration and epithelial-to-mesenchymal transition (EMT). Electroporation of constructs that modulate cVICKZ expression demonstrates that this down-regulation is both necessary and sufficient for CNC EMT. These results suggest that VICKZ down-regulation in CNC cell-autonomously promotes EMT and migration. Reduction of VICKZ throughout the embryo, however, inhibits CNC migration non-cell-autonomously, as judged by transplantation experiments in Xenopus embryos. Given the positive role reported for VICKZ proteins in promoting cell migration of chick embryo fibroblasts and many types of cancer cells, we have begun to look for specific mRNAs that could mediate context-specific differences. We report here that the laminin receptor, integrin alpha 6, is down-regulated in the dorsal neural tube when CNC cells emigrate, this process is mediated by cVICKZ, and integrin alpha 6 mRNA is found in VICKZ ribonucleoprotein complexes. Significantly, prolonged inhibition of cVICKZ in either the neural tube or the nascent dermomyotome sheet, which also dynamically expresses cVICKZ, induces disruption of these epithelia. These data point to a previously unreported role for VICKZ in maintaining epithelial integrity.