The ErbB2 and ErbB3 receptors and their ligand, neuregulin-1, are essential for development of the sympathetic nervous system

S Britsch, L Li, S Kirchhoff, F Theuring, V Brinkmann, C Birchmeier, D Riethmacher

    Research output: Contribution to journalArticleAcademicpeer-review


    Neuregulins (NDF, heregulin, GGF ARIA, or SMDF) are EGF-like growth and differentiation factors that signal through tyrosine kinase receptors of the ErbB family. Here, we report a novel phenotype in mice with targeted mutations in the erbB2, erbB3, or neuregulin-1 genes. These three mutations cause a severe hypoplasia of the primary sympathetic ganglion chain. We provide evidence that migration of neural crest cells to the mesenchyme lateral of the dorsal aorta, in which they differentiate into sympathetic neurons, depends on neuregulin-1 and its receptors. Neuregulin-1 is expressed at the origin of neural crest cells. Moreover, a tight link between neuregulin-1 expression, the migratory path, and the target site of sympathogenic neural crest cells is observed. Sympathetic ganglia synthesize catecholamines in the embryo and the adult. Accordingly, catecholamine levels in mutant embryos are severely decreased, and we suggest that the lack of catecholamines contributes to the embryonal lethality of the erbB3 mutant mice. Thus, neuregulin-1, erbB2, and erbB3 are required for the formation of the sympathetic nervous system; the block in development observed in mutant mice is caused by a lack of neural crest precursor cells in the anlage of the primary sympathetic ganglion chain. Together with previous observations, these findings establish the neuregulin signaling system as a key regulator in the development of neural crest cells.

    Original languageEnglish
    Pages (from-to)1825-36
    Number of pages12
    JournalGenes and Development
    Issue number12
    Publication statusPublished - 15 Jun 1998


    • Animals
    • Antineoplastic Agents
    • Aorta
    • Cell Movement
    • Embryo, Mammalian
    • Ganglia, Spinal
    • Gene Expression
    • Genes
    • Genes, erbB-2
    • Glycoproteins
    • Ligands
    • Mesoderm
    • Mice
    • Mice, Inbred C57BL
    • Mice, Inbred Strains
    • Mutation
    • Nerve Growth Factors
    • Neural Crest
    • Neuregulins
    • Phenotype
    • Proto-Oncogene Proteins
    • Receptor, Epidermal Growth Factor
    • Receptor, ErbB-2
    • Receptor, ErbB-3
    • Signal Transduction
    • Sympathetic Nervous System
    • Time Factors


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