Defects in pathfinding by cranial neural crest cells in mice lacking the neuregulin receptor ErbB4.
Mouse embryos with a loss-of-function mutation in the gene encoding the receptor tyrosine kinase ErbB4 exhibit misprojections of cranial sensory ganglion afferent axons. Here we analyse ErbB4-deficient mice, and find that morphological differences between wild-type and mutant cranial ganglia correlate with aberrant migration of a subpopulation of hindbrain-derived cranial neural crest cells within the paraxial mesenchyme environment. In transplantation experiments using new grafting techniques in cultured mouse embryos, we determine that this phenotype is non-cell-autonomous: wild-type and mutant neural crest cells both migrate in a pattern consistent with the host environment, deviating from their normal pathway only when transplanted into mutant embryos. ErbB4 signalling events within the hindbrain therefore provide patterning information to cranial paraxial mesenchyme that is essential for the proper migration of neural crest cells.
Golding
J P
JP
Division of Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Trainor
P
P
Krumlauf
R
R
Gassmann
M
M
D000818:Animals; D019521:Body Patterning; D001934:Branchial Region / Q000196:embryology; D002465:Cell Movement; D004423:Ear / Q000196:embryology; D004627:Embryonic Induction; D066246:ErbB Receptors / Q000235:genetics*; D017950:Ganglia, Sensory / Q000196:embryology; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009432:Neural Crest / Q000196:embryology*; D020880:Neuregulins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D066247:Receptor, ErbB-4; D012249:Rhombencephalon / Q000196:embryology*; D015398:Signal Transduction; D016378:Tissue Transplantation
D020880:Neuregulins; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D066247:Receptor, ErbB-4