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

Nature volume 399, pages 366–370 (1999)Cite this article

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 subunits9,10,11,12, 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-β-hydroxylase and tyrosine hydroxylase, demonstrating that Phox2b regulates the noradrenergic phenotype in vertebrates.

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Figure 1: Targeted disruption of the Phox2b gene.
Figure 2: Absence of the sympathetic, parasympathetic and enteric components of the autonomic nervous system in E13.5 Phox2b LacZ/LacZ embryos.
Figure 3: Early formation and degeneration of the sympathetic chain and the foregut enteric nervous system in Phox2b LacZ/LacZ mice.
Figure 4: Altered gene expression in the early sympathetic chain of Phox2b LacZ/LacZ embryos.
Figure 5: Altered gene expression in foregut enteric-neuron precursors at E10.5.
Figure 6: Formation and atrophy of placode-derived cranial ganglia VII, IX and X in Phox2bLacZ/LacZ mice.

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Acknowledgements

We thank the following for probes: V. Pachnis (Ret), M. Wegner (Sox10), F.Guillemot (Mash1), C. Birchmeier (ErbB3); and M.-M. Portier (peripherin). This work was supported by institutional grants from the CNRS and Université de la Méditerranée and by specific grants from the European Community Biotech programme, the Association Française contre les Myopathies, the Association pour la Recherche sur le Cancer and Rhône-Poulenc S.A.

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  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, Marseille, Cedex 9, 13288, France

    Alexandre Pattyn, Xavier Morin, Harold Cremer, Christo Goridis & Jean-FranÇois Brunet

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  1. Alexandre Pattyn
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  2. Xavier Morin
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  3. Harold Cremer
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  4. Christo Goridis
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  5. Jean-FranÇois Brunet
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Correspondence to Jean-FranÇois Brunet.

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Pattyn, A., Morin, X., Cremer, H. et al. The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives. Nature 399, 366–370 (1999). https://doi.org/10.1038/20700

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