The role of SF/HGF and c-Met in the development of skeletal muscle

Susanne Dietrich, Faikah Abou-Rebyeh, Henning Brohmann, Friedhelm Bladt, Eva Sonnenberg-Riethmacher, Tomoichiro Yamaai, Andrew Lumsden, Beate Brand-Saberi, Carmen Birchmeier

Research output: Contribution to journalArticlepeer-review

235 Citations (Scopus)

Abstract

Hypaxial skeletal muscles develop from migratory and non-migratory precursor cells that are generated by the lateral lip of the dermomyotome. Previous work shows that the formation of migratory precursors requires the c-Met and SF/HGF genes. We show here that in mice lacking c-Met or SF/HGF, the initial development of the dermomyotome proceeds appropriately and growth and survival of cells in the dermomyotome are not affected. Migratory precursors are also correctly specified, as monitored by the expression of Lbx1. However, these cells remain aggregated and fail to take up long range migration. We conclude that parallel but independent cues converge on the migratory hypaxial precursors in the dermomyotomal lip after they are laid down: a signal given by SF/HGF that controls the emigration of the precursors, and an as yet unidentified signal that controls Lbx1. SF/HGF and c-Met act in a paracrine manner to control emigration, and migratory cells only dissociate from somites located close to SF/HGF-expressing cells. During long range migration, prolonged receptor-ligand-interaction appears to be required, as SF/HGF is expressed both along the routes and at the target sites of migratory myogenic progenitors. Mice that lack c-Met die during the second part of gestation due to a placental defect. Rescue of the placental defect by aggregation of tetraploid (wild type) and diploid (c-Met(-/-)) morulae allows development of c-Met mutant animals to term. They lack muscle groups that derive from migratory precursor cells, but display otherwise normal skeletal musculature.

Original languageEnglish
Pages (from-to)1621-1629
Number of pages9
JournalDevelopment
Volume126
Issue number8
Publication statusPublished - Apr 1 1999

Keywords

  • Cell migration
  • Hepatocyte growth factor
  • Hypaxial muscle
  • Lbx1
  • Mouse
  • Pax3
  • Scatter factor
  • c-Met

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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