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

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  • Alexandre Pattyn

    (Laboratoire de Génétique et Physiologie du Développement, Developmental Biology Institute of Marseille, CNRS/INSERM/Université de la Méditterraneé/AP de Marseille)

  • Xavier Morin

    (Laboratoire de Génétique et Physiologie du Développement, Developmental Biology Institute of Marseille, CNRS/INSERM/Université de la Méditterraneé/AP de Marseille)

  • Harold Cremer

    (Laboratoire de Génétique et Physiologie du Développement, Developmental Biology Institute of Marseille, CNRS/INSERM/Université de la Méditterraneé/AP de Marseille)

  • Christo Goridis

    (Laboratoire de Génétique et Physiologie du Développement, Developmental Biology Institute of Marseille, CNRS/INSERM/Université de la Méditterraneé/AP de Marseille)

  • Jean-FranÇois Brunet

    (Laboratoire de Génétique et Physiologie du Développement, Developmental Biology Institute of Marseille, CNRS/INSERM/Université de la Méditterraneé/AP de Marseille)

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.

Suggested Citation

  • Alexandre Pattyn & Xavier Morin & Harold Cremer & Christo Goridis & Jean-FranÇois Brunet, 1999. "The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives," Nature, Nature, vol. 399(6734), pages 366-370, May.
    • Handle: RePEc:nat:nature:v:399:y:1999:i:6734:d:10.1038_20700
    DOI: 10.1038/20700
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    1. Bowen Dempsey & Selvee Sungeelee & Phillip Bokiniec & Zoubida Chettouh & Séverine Diem & Sandra Autran & Evan R. Harrell & James F. A. Poulet & Carmen Birchmeier & Harry Carey & Auguste Genovesio & Si, 2021. "A medullary centre for lapping in mice," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Anna Laddach & Song Hui Chng & Reena Lasrado & Fränze Progatzky & Michael Shapiro & Alek Erickson & Marisol Sampedro Castaneda & Artem V. Artemov & Ana Carina Bon-Frauches & Eleni-Maria Amaniti & Jens, 2023. "A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Marta Ditmer & Szymon Turkiewicz & Agata Gabryelska & Marcin Sochal & Piotr Białasiewicz, 2021. "Adolescent Congenital Central Hypoventilation Syndrome: An Easily Overlooked Diagnosis," IJERPH, MDPI, vol. 18(24), pages 1-13, December.

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