| Summary: | <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">The neural crest is an embryonic population of migratory, multipotent cells that are formed at the boundary of the neural and non-neural ectoderm around the time of neural tube closure. After migrating to locations throughout the embryo the neural crest cells differentiate into many different cell types including osteoblasts and chondrocytes of the cranio-facial skeleton and neurones and glia of the peripheral nervous system. Gain of function experiments demonstrate that many genes, including the <em>Zic</em> gene family, are involved in neural crest formation. In order to determine whether they have a role in endogenous neural crest development, loss of function studies are required. The ability to perform genetic analysis in the mouse makes it an ideal organism in which to do this.</p> <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">When this study commenced <em>Zic1</em>, <em>Zic2</em> and <em>Zic3</em> were assigned as members of the mammalian <em>Zic</em> gene family. A comparison of their expression patterns during mouse neural crest development reveals <em>Zic2</em> and <em>Zic3</em> to be the most likely to have roles in neural crest formation. Analysis of neural crest induction and migration in loss of function alleles of <em>Zic2</em> and <em>Zic3</em> reveals that loss of either gene function alone causes both a delay in the onset of trunk neural crest production and a reduction in the number of neural crest progenitor cells. Additionally, loss of <em>Zic2</em> gene function results in a heightened response to BMP signalling by the neural tube. A more severe neural crest depletion occurs in embryos lacking <em>Zic3</em> and heterozygous for a mutation in <em>Zic2</em>. These results indicate that <em>Zic2</em> and <em>Zic3</em> cooperate in the formation of the neural crest by mediating the competence of the dorsal neural tube to respond to inductive signals. This work provides the first genetic evidence that <em>Zic2</em> and <em>Zic3</em> are involved in neural crest development and that they function together during mouse development.</p>
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