title: Selective regulation of nerve growth factor expression in developing cutaneous tissue by early sensory innervation.
abstract: BACKGROUND
  In the developing vertebrate peripheral nervous system, the survival of sympathetic neurons and the majority of sensory neurons depends on a supply of nerve growth factor (NGF) from tissues they innervate. Although neurotrophic theory presupposes, and the available evidence suggests, that the level of NGF expression is completely independent of innervation, the possibility that innervation may regulate the timing or level of NGF expression has not been rigorously investigated in a sufficiently well-characterized developing system.
  
  
  RESULTS
  To address this important question, we studied the influence of innervation on the regulation of NGF mRNA expression in the embryonic mouse maxillary process in vitro and in vivo. The maxillary process receives its innervation from predominantly NGF-dependent sensory neurons of the trigeminal ganglion and is the most densely innervated cutaneous territory with the highest levels of NGF in the embryo. When early, uninnervated maxillary processes were cultured alone, the level of NGF mRNA rose more slowly than in maxillary processes cultured with attached trigeminal ganglia. In contrast to the positive influence of early innervation on NGF mRNA expression, the levels of brain-derived neurotrophic factor (BDNF) mRNA and neurotrophin-3 (NT3) mRNA rose to the same extent in early maxillary processes grown with and without trigeminal ganglia. The level of NGF mRNA, but not BDNF mRNA or NT3 mRNA, was also significantly lower in the maxillary processes of erbB3-/- mice, which have substantially fewer trigeminal neurons than wild-type mice.
  
  
  CONCLUSIONS
  This selective effect of initial innervation on target field NGF mRNA expression provokes a re-evaluation of a key assertion of neurotrophic theory that the level of NGF expression is independent of innervation.
authors.affiliation: Molecular Biosciences Research Division, Life Sciences Building, School of Biosciences, Museum Avenue, Cardiff CF10 3AT, UK.
authors.forename: Sean L
authors.initials: SL
authors.lastname: Wyatt
authors.forename: Bodo
authors.initials: B
authors.lastname: Spori
authors.forename: Tom N
authors.initials: TN
authors.lastname: Vizard
authors.forename: Alun M
authors.initials: AM
authors.lastname: Davies
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000172:deficiency; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D012867:Skin / Q000294:innervation*; D012668:Trigeminal Ganglion / Q000166:cytology* / Q000196:embryology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D020893:Receptor, ErbB-3; D020917:Receptor, trkA; D020812:Receptor, trkC