RESUMEN
Activation of the RET receptor tyrosine kinase by glial-derived neurotrophic factor family members is dependent on a family of coreceptors, GFRalpha1-4. GFRalpha3 preferentially binds the newest member of the glial-derived neurotrophic factor family of ligands, artemin. The major site of GFRalpha3 expression is in the dorsal root ganglion; however, the class of sensory neurons that expresses GFRalpha3 has not been reported previously. Using immunohistochemical methods, we show that the majority of dorsal root ganglion cells that express GFRalpha3 also express vanilloid receptor type 1, peripherin, RET, trkA and calcitonin gene-related peptide. In addition, a significant subpopulation of GFRalpha3-expressing cells also binds the lectin IB4. We demonstrate that GFRalpha3 artemin neurons are immunopositive for markers expected of nociceptors and include a subset of neurons distinct from the GDNF-responsive population. Our results indicate artemin may exert selective effects on pain sensation.
Asunto(s)
Proteínas de Drosophila , Ganglios Espinales/metabolismo , Glicoproteínas de Membrana , Neuronas Aferentes/metabolismo , Nociceptores/metabolismo , Dolor/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores de Factor de Crecimiento Nervioso , Animales , Biomarcadores , Péptido Relacionado con Gen de Calcitonina/metabolismo , Femenino , Ganglios Espinales/citología , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial , Inmunohistoquímica , Proteínas de Filamentos Intermediarios/metabolismo , Lectinas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/metabolismo , Proteínas de Neurofilamentos/metabolismo , Neuronas Aferentes/citología , Nociceptores/citología , Dolor/fisiopatología , Periferinas , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-ret , Ratas , Ratas Sprague-Dawley , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptor trkA/metabolismo , Receptores de Droga/metabolismoAsunto(s)
Proteínas Morfogenéticas Óseas/genética , Patos/embriología , Pie/embriología , Expresión Génica , Miembro Posterior/embriología , Factor de Crecimiento Transformador beta , Animales , Proteína Morfogenética Ósea 2 , Proteína Morfogenética Ósea 4 , Proteína Morfogenética Ósea 7 , Patos/genética , Miembro Posterior/metabolismo , Hibridación in Situ , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
The apical ectodermal ridge of the vertebrate limb bud lies at the junction of the dorsal and ventral ectoderm and directs patterning of the growing limb. Its formation is directed by the boundary between cells that do and cells that do not express the gene Radical fringe. This is similar to the establishment of the margin cells at the Drosophila wing dorsoventral border by fringe. Radical fringe expression in chick-limb dorsal ectoderm is established in part through repression by Engrailed-1 in the ventral ectoderm.