Schematic representation of the effect of aberrant Phox2b on sympathetic neuronal development in the zebrafish model.

Abstract

<p>Phox2b is the master regulator of a differentiation cascade involving <i>Hand2</i>, <i>Gata2/3</i> and <i>Tfap2a</i> that ultimately leads to terminal differentiation of neuron progenitors, marked by <i>dbh</i> and <i>th</i> expression. Phox2b regulates itself as well as <i>ascl1a</i> and can directly activate <i>dbh</i>. A decreased dosage of the <i>phox2b</i> gene, either by allelic deletion (Phox2b KD) or by dominant-negative mutations (<i>676delG</i> or <i>K155X</i>) can compromise normal Phox2b function so that the cells are unable to progress through the various developmental stages and instead remain in an undifferentiated state.</p