A novel role for VICKZ proteins in maintaining epithelial integrity during embryogenesis

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Abstract

Background: 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. Results and Conclusions: 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.

Original languageAmerican English
Article numbere0136408
Number of pages21
JournalPLoS ONE
Volume10
Issue number8
DOIs
StatePublished - 28 Aug 2015

Bibliographical note

Funding Information:
We would like to thank the members of the Yisraeli, Kalcheim, and Sela-Donenfeld labs for helpful discussions, ideas, reagents, and support. We would also like to thank Rob Singer for the cVICKZ1 and Y396F constructs. We are very grateful to Doris Wedlich at the Karlsruhe Institute for Technology, and Jubin Kashef and Almut Köhler in her lab, for teaching MSC the Xenopus CNC transplantation technique and for assistance with the experiments. MSC gratefully acknowledges the support of the Company of Biologists for the travel fellowship to Karlsruhe. This work was supported in part by a grant from the Israel Academy of Sciences (JKY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2015 Carmel et al.

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