Peripheral nervous system defects in erbB2 mutants following genetic rescue of heart development

Masresha T. Woldeyesus, Stefan Britsch, Dieter Riethmacher, Lan Xu, Eva Sonnenberg-Riethmacher, Faikah Abou-Rebyeh, Richard Harvey, Pico Caroni, Carmen Birchmeier

Research output: Contribution to journalArticle

195 Citations (Scopus)

Abstract

The ErbB2 tyrosine kinase functions as coreceptor for the neuregulin receptors ErbB3 and ErbB4 and can participate in signaling of EGF receptor (ErbB1), interleukin receptor gp130, and G-protein coupled receptors. ErbB2- 1- mice die at midgestation because of heart malformation. Here, we report a genetic rescue of their heart development by myocardial expression of erbB2 cDNA that allows survival of the mutants to birth. In rescued erbB2 mutants, Schwann cells are lacking. Motoneurons form and can project to muscle, but nerves are poorly fasciculated and disorganized. Neuromuscular junctions form, as reflected in clustering of AChR and postsynaptic expression of the genes encoding the α-AChR, ACHE, ε-AChR, and the RI subunit of the cAMP protein kinase. However, a severe loss of motoneurons on cervical and lumbar, but not on thoracic levels occurs. Our results define the roles of Schwann cells during motoneuron and synapse development, and reveal different survival requirements for distinct motoneuron populations.

Original languageEnglish
Pages (from-to)2538-2548
Number of pages11
JournalGenes and Development
Volume13
Issue number19
DOIs
Publication statusPublished - Oct 1 1999
Externally publishedYes

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Peripheral Nervous System
Motor Neurons
Schwann Cells
Neuregulins
Interleukin Receptors
Congenital Heart Defects
Neuromuscular Junction
G-Protein-Coupled Receptors
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Synapses
Protein Kinases
Cluster Analysis
Thorax
Complementary DNA
Parturition
Gene Expression
Muscles
Population

Keywords

  • AChR
  • Coreceptor
  • Motoneuron loss
  • Neuregulin
  • Neuromuscular synapse

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Peripheral nervous system defects in erbB2 mutants following genetic rescue of heart development. / Woldeyesus, Masresha T.; Britsch, Stefan; Riethmacher, Dieter; Xu, Lan; Sonnenberg-Riethmacher, Eva; Abou-Rebyeh, Faikah; Harvey, Richard; Caroni, Pico; Birchmeier, Carmen.

In: Genes and Development, Vol. 13, No. 19, 01.10.1999, p. 2538-2548.

Research output: Contribution to journalArticle

Woldeyesus, MT, Britsch, S, Riethmacher, D, Xu, L, Sonnenberg-Riethmacher, E, Abou-Rebyeh, F, Harvey, R, Caroni, P & Birchmeier, C 1999, 'Peripheral nervous system defects in erbB2 mutants following genetic rescue of heart development', Genes and Development, vol. 13, no. 19, pp. 2538-2548. https://doi.org/10.1101/gad.13.19.2538
Woldeyesus, Masresha T. ; Britsch, Stefan ; Riethmacher, Dieter ; Xu, Lan ; Sonnenberg-Riethmacher, Eva ; Abou-Rebyeh, Faikah ; Harvey, Richard ; Caroni, Pico ; Birchmeier, Carmen. / Peripheral nervous system defects in erbB2 mutants following genetic rescue of heart development. In: Genes and Development. 1999 ; Vol. 13, No. 19. pp. 2538-2548.
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