RESUMEN
Neuropilins are receptors for class 3 secreted semaphorins, most of which can function as potent repulsive axon guidance cues. We have generated mice with a targeted deletion in the neuropilin-2 (Npn-2) locus. Many Npn-2 mutant mice are viable into adulthood, allowing us to assess the role of Npn-2 in axon guidance events throughout neural development. Npn-2 is required for the organization and fasciculation of several cranial nerves and spinal nerves. In addition, several major fiber tracts in the brains of adult mutant mice are either severely disorganized or missing. Our results show that Npn-2 is a selective receptor for class 3 semaphorins in vivo and that Npn-1 and Npn-2 are required for development of an overlapping but distinct set of CNS and PNS projections.
Asunto(s)
Axones/fisiología , Proteínas Portadoras/metabolismo , Glicoproteínas/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Factores de Edad , Animales , Axones/química , Química Encefálica/fisiología , Células COS , Eliminación de Gen , Regulación del Desarrollo de la Expresión Génica , Habénula/química , Habénula/embriología , Habénula/patología , Ratones , Ratones Noqueados , Fibras Musgosas del Hipocampo/química , Fibras Musgosas del Hipocampo/embriología , Fibras Musgosas del Hipocampo/patología , Neuronas Motoras/química , Neuronas Motoras/fisiología , Neuronas Motoras/ultraestructura , Neuropilina-1 , Sistema Nervioso Periférico/química , Sistema Nervioso Periférico/embriología , Sistema Nervioso Periférico/patología , Unión Proteica/fisiología , Ratas , Semaforina-3A , Nervios Espinales/química , Nervios Espinales/patología , Nervios Espinales/fisiología , Ganglio Cervical Superior/química , Ganglio Cervical Superior/embriología , Ganglio Cervical Superior/patología , Tálamo/química , Tálamo/embriología , Tálamo/patología , Nervio Troclear/química , Nervio Troclear/embriología , Nervio Troclear/patologíaRESUMEN
The presence of internuclear neurons in the abducens and oculomotor nuclei of lampreys [González, M.J., Pombal, M.A., Rodicio, M.C. and Anadón, R., Internuclear neurons of the ocular motor system of the larval sea lamprey, J. Comp. Neurol. 401 (1998) 1-15] indicates that coordination of eye movements by internuclear neurons appeared early during the evolution of vertebrates. In order to investigate the possible involvement of inhibitory neurotransmitters in internuclear circuits, the distribution of gamma-aminobutyric acid (GABA) in the extraocular motor nuclei of the lamprey was studied using immunocytochemical techniques. Small GABA-immunoreactive (GABAir) neurons were observed in the three ocular motor nuclei. Numerous GABAir neurons were observed in the group of internuclear neurons of the dorsal rectus oculomotor subnucleus. A second group of GABAir neurons was observed among and below the trochlear motoneurons. Two further groups of GABAir interneurons, periventricular and lateral, were located in the abducens nucleus among the cells of the caudal rectus and the ventral rectus motor subnuclei, respectively. In addition to the presence of GABAir neurons, in all the ocular motor nuclei the motoneurons were contacted by numerous GABAir boutons. Taken together, these results suggest that GABA is involved as a neurotransmitter in internuclear pathways of the ocular motor system of lampreys.
Asunto(s)
Nervios Craneales/química , Nervios Craneales/citología , Interneuronas/química , Ácido gamma-Aminobutírico/análisis , Nervio Abducens/química , Nervio Abducens/citología , Factores de Edad , Animales , Anticuerpos , Lampreas , Larva , Neuronas Motoras/química , Nervio Oculomotor/química , Nervio Oculomotor/citología , Nervio Troclear/química , Nervio Troclear/citología , Ácido gamma-Aminobutírico/inmunologíaRESUMEN
After treatment of melanomas with anti-GD2 monoclonal antibody (MAb) (14G2a), some patients develop sensorimotor demyelinating polyneuropathy with and without the syndrome of inappropriate antidiuretic hormone (SIADH). To clarify what causes the neurotoxicity of anti-GD2 MAb, we investigated the immunohistochemical localization of GD2 in the human nervous system. Anti-GD2 MAb (14G2a) reacted with the myelin sheaths in the peripheral nerves as well as with the pituicyte cytoplasm in the posterior lobe of the pituitary gland. We assume that the binding of anti-GD2 MAb to peripheral nerve myelin and the pituicytes in the posterior pituitary causes sensorimotor demyelinating neuropathy and SIADH.