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      Meis2 is essential for cranial and cardiac neural crest development

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          Abstract

          Background

          TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a conditional allele of Meis2 in mice and shown that systemic inactivation of the Meis2 gene results in lethality by the embryonic day 14 that is accompanied with hemorrhaging.

          Results

          We show that neural crest cells express Meis2 and Meis2-defficient embryos display defects in tissues that are derived from the neural crest, such as an abnormal heart outflow tract with the persistent truncus arteriosus and abnormal cranial nerves. The importance of Meis2 for neural crest cells is further confirmed by means of conditional inactivation of Meis2 using crest-specific AP2α-IRES-Cre mouse. Conditional mutants display perturbed development of the craniofacial skeleton with severe anomalies in cranial bones and cartilages, heart and cranial nerve abnormalities.

          Conclusions

          Meis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12861-015-0093-6) contains supplementary material, which is available to authorized users.

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          Most cited references40

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          A gene regulatory network orchestrates neural crest formation.

          The neural crest is a multipotent, migratory cell population that is unique to vertebrate embryos and gives rise to many derivatives, ranging from the peripheral nervous system to the craniofacial skeleton and pigment cells. A multimodule gene regulatory network mediates the complex process of neural crest formation, which involves the early induction and maintenance of the precursor pool, emigration of the neural crest progenitors from the neural tube via an epithelial to mesenchymal transition, migration of progenitor cells along distinct pathways and overt differentiation into diverse cell types. Here, we review our current understanding of these processes and discuss the molecular players that are involved in the neural crest gene regulatory network.
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            Development and evolution of the neural crest: an overview.

            The neural crest is a multipotent and migratory cell type that forms transiently in the developing vertebrate embryo. These cells emerge from the central nervous system, migrate extensively and give rise to diverse cell lineages including melanocytes, craniofacial cartilage and bone, peripheral and enteric neurons and glia, and smooth muscle. A vertebrate innovation, the gene regulatory network underlying neural crest formation appears to be highly conserved, even to the base of vertebrates. Here, we present an overview of important concepts in the neural crest field dating from its discovery 150 years ago to open questions that will motivate future research. Copyright © 2012. Published by Elsevier Inc.
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              • Record: found
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              Cranial neural crest and the building of the vertebrate head.

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                Author and article information

                Contributors
                machon@img.cas.cz
                jan.masek@img.cas.cz
                olga.machonova@img.cas.cz
                stefan.krauss@rr-research.no
                zbynek.kozmik@img.cas.cz
                Journal
                BMC Dev Biol
                BMC Dev. Biol
                BMC Developmental Biology
                BioMed Central (London )
                1471-213X
                6 November 2015
                6 November 2015
                2015
                : 15
                : 40
                Affiliations
                [ ]Institute of Molecular Genetics, The Czech Academy of Sciences, 14200 Praha, Czech Republic
                [ ]Unit for Cell Signaling, Oslo University Hospital, N-0349 Oslo, Norway
                Article
                93
                10.1186/s12861-015-0093-6
                4636814
                26545946
                0b36b703-197d-4523-abd2-7fa315f6ef91
                © Machon et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 11 August 2015
                : 3 November 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Developmental biology
                meis2,neural crest,persistent truncus arteriosus,craniofacial skeleton,cranial nerves

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