The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives

The sympathetic, parasympathetic and enteric ganglia are the main component s of the peripheral autonomic nervous system(1), and are all derived from t he neural crest(2). The factors needed for these structures to develop incl ude the transcription factor Mash 1 (refs 3-5), the glial-derived neurotrop hic factor GNDF (refs 6-8) and its receptor subunits(9-12), and the neuregu lin signalling system(13), each of which is essential for the differentiati on and survival of subsets of autonomic neurons. Here we show that all auto nomic ganglia fail to form properly and degenerate in mice lacking the home odomain transcription factor Phox2b, as do the three cranial sensory gangli a that are part of the autonomic reflex circuits. in the anlagen of the ent eric nervous system and the sympathetic ganglia, Phox2b is needed for the e xpression of the GDNF-receptor subunit Ret and for maintaining Mash1 expres sion. Mutant ganglionic anlagen also fail to switch on the genes that encod e two enzymes needed for the biosynthesis of the neurotransmitter noradrena line, dopamine-beta-hydroxylase and tyrosine hydroxylase, demonstrating tha t Phox2b regulates the noradrenergic phenotype in vertebrates.