title: Members of the BMP, Shh, and FGF morphogen families promote chicken statoacoustic ganglion neurite outgrowth and neuron survival in vitro.
abstract: Mechanosensory hair cells of the chicken inner ear are innervated by the peripheral processes of statoacoustic ganglion (SAG) neurons. Members of several morphogen families are expressed within and surrounding the chick inner ear during stages of SAG axon outgrowth and pathfinding. On the basis of their localized expression patterns, we hypothesized that bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs), and sonic hedgehog (Shh) may function as guidance cues for growing axons and/or may function as trophic factors once axons have reached their targets. To test this hypothesis, three-dimensional collagen cultures were used to grow Embryonic Day 4 (E4) chick SAG explants for 24 h in the presence of purified proteins or beads soaked in proteins. The density of neurite outgrowth was quantified to determine effects on neurite outgrowth. Explants displayed enhanced neurite outgrowth when cultured in the presence of purified BMP4, BMP7, a low concentration of Shh, FGF8, FGF10, or FGF19. In contrast, SAG neurons appeared unresponsive to FGF2. Collagen gel cultures were labeled with terminal dUTP nick-end labeling and immunostained with anti-phosphohistone H3 to determine effects on neuron survival and proliferation, respectively. Treatments that increased neurite outgrowth also yielded significantly fewer apoptotic cells, with no effect on cell proliferation. When presented as focal sources, BMP4, Shh, and FGFs -8, -10, and -19 promoted asymmetric outgrowth from the ganglion in the direction of the beads. BMP7-soaked beads did not induce this response. These results suggest that a subset of morphogens enhance both survival and axon outgrowth of otic neurons.
authors: Department of Biological Sciences and Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907-1392, USA.
authors: Kristen N
authors: KN
authors: Fantetti
authors: Donna M
authors: DM
authors: Fekete
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002642:Chick Embryo; D002645:Chickens; D018920:Coculture Techniques; D005346:Fibroblast Growth Factors / Q000494:pharmacology / Q000502:physiology*; D053823:Hedgehog Proteins / Q000494:pharmacology / Q000502:physiology*; D016501:Neurites / Q000502:physiology*; D009924:Organ Culture Techniques; D061251:Primary Cell Culture; D013136:Spiral Ganglion / Q000166:cytology* / Q000187:drug effects / Q000196:embryology; D014725:Vestibular Nerve / Q000166:cytology* / Q000187:drug effects / Q000196:embryology
chemical_list: D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D005346:Fibroblast Growth Factors