1. Laboratoire de Génétique et Physiologie du Développement, Developmental Biology Institute of Marseille, CNRS/INSERM/Université de la Méditterraneé/AP de Marseille, Luminy Case 907, 13288 Marseille Cedex 9, France

Correspondence to: Jean-FranÇois Brunet Correspondence and requests for materials should be addressed to J.-F.B. (e-mail: Email: brunet@ibdm.univ-mrs.fr).

Abstract

The sympathetic, parasympathetic and enteric ganglia are the main components of the peripheral autonomic nervous system¹, and are all derived from the neural crest². The factors needed for these structures to develop include the transcription factor Mash1 (refs 3,4,5), the glial-derived neurotrophic factor GNDF (refs 6,7,8) and its receptor subunits^{9, 10, 11, 12}, and the neuregulin signalling system¹³, each of which is essential for the differentiation and survival of subsets of autonomic neurons. Here we show that all autonomic ganglia fail to form properly and degenerate in mice lacking the homeodomain transcription factor Phox2b, as do the three cranial sensory ganglia that are part of the autonomic reflex circuits. In the anlagen of the enteric nervous system and the sympathetic ganglia, Phox2b is needed for the expression of the GDNF-receptor subunit Ret and for maintaining Mash1 expression. Mutant ganglionic anlagen also fail to switch on the genes that encode two enzymes needed for the biosynthesis of the neurotransmitter noradrenaline, dopamine--hydroxylase and tyrosine hydroxylase, demonstrating that Phox2b regulates the noradrenergic phenotype in vertebrates.