Regulatory genetic network for control of growth and morphogenesis in the pharyngeal arches by edn1 and hand2.

<p>(A) The model assumes that regulation of early proliferation in the ventral arches, in which <i>edn1</i> is epistatic to <i>hand2,</i> can account for the DV extension phenotype explored in this study. The positive pathway regulating patterning and late outgrowth accounts for the general reduction of elements in the ventral skeleton, as well skeletal disruption because of downregulation of downsteam patterning genes studied elsewhere <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067522#pone.0067522-Talbot1" target="_blank">[10]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067522#pone.0067522-Miller2" target="_blank">[12]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067522#pone.0067522-Walker1" target="_blank">[23]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067522#pone.0067522-Nichols1" target="_blank">[24]</a>. This model predicts a temporally dynamic switching in <i>hand2</i> function, from negative to positive, which can be explored in future studies. (B) We propose <i>hand2</i> negatively regulates the anterior extension movement in the ventral first arch independent of <i>edn1</i> function.