SF/HGF is a mediator between limb patterning and muscle development.
Scatter factor/hepatocyte growth factor (SF/HGF) is known to be involved in the detachment of myogenic precursor cells from the lateral dermomyotomes and their subsequent migration into the newly formed limb buds. As yet, however, nothing has been known about the role of the persistent expression of SF/HGF in the limb bud mesenchyme during later stages of limb bud development. To test for a potential role of SF/HGF in early limb muscle patterning, we examined the regulation of SF/HGF expression in the limb bud as well as the influence of SF/HGF on direction control of myogenic precursor cells in limb bud mesenchyme. We demonstrate that SF/HGF expression is controlled by signals involved in limb bud patterning. In the absence of an apical ectodermal ridge (AER), no expression of SF/HGF in the limb bud is observed. However, FGF-2 application can rescue SF/HGF expression. Excision of the zone of polarizing activity (ZPA) results in ectopic and enhanced SF/HGF expression in the posterior limb bud mesenchyme. We could identify BMP-2 as a potential inhibitor of SF/HGF expression in the posterior limb bud mesenchyme. We further demonstrate that ZPA excision results in a shift of Pax-3-positive cells towards the posterior limb bud mesenchyme, indicating a role of the ZPA in positioning of the premuscle masses. Moreover, we present evidence that, in the limb bud mesenchyme, SF/HGF increases the motility of myogenic precursor cells and has a role in maintaining their undifferentiated state during migration. We present a model for a crucial role of SF/HGF during migration and early patterning of muscle precursor cells in the vertebrate limb.
Scaal
M
M
Institute of Anatomy, University of Freiburg, Albertstrasse 17, D-79104 Freiburg, Germany. brandsab@uni-freiburg.de.
Bonafede
A
A
Dathe
V
V
Sachs
M
M
Cann
G
G
Christ
B
B
Brand-Saberi
B
B
D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002642:Chick Embryo; D003370:Coturnix / Q000196:embryology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004475:Ectoderm / Q000502:physiology; D004625:Embryo, Nonmammalian; D004627:Embryonic Induction / Q000235:genetics; D005121:Extremities / Q000196:embryology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D018878:Limb Buds / Q000166:cytology / Q000187:drug effects; D008648:Mesoderm / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology*; D009154:Mutation; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology; D013234:Stem Cells; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D011506:Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; C068686:Pax3 protein, mouse; D017228:Hepatocyte Growth Factor