RESUMO
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.
Assuntos
Axônios/fisiologia , Proteínas de Transporte/metabolismo , Glicoproteínas/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fatores Etários , Animais , Axônios/química , Química Encefálica/fisiologia , Células COS , Deleção de Genes , Regulação da Expressão Gênica no Desenvolvimento , Habenula/química , Habenula/embriologia , Habenula/patologia , Camundongos , Camundongos Knockout , Fibras Musgosas Hipocampais/química , Fibras Musgosas Hipocampais/embriologia , Fibras Musgosas Hipocampais/patologia , Neurônios Motores/química , Neurônios Motores/fisiologia , Neurônios Motores/ultraestrutura , Neuropilina-1 , Sistema Nervoso Periférico/química , Sistema Nervoso Periférico/embriologia , Sistema Nervoso Periférico/patologia , Ligação Proteica/fisiologia , Ratos , Semaforina-3A , Nervos Espinhais/química , Nervos Espinhais/patologia , Nervos Espinhais/fisiologia , Gânglio Cervical Superior/química , Gânglio Cervical Superior/embriologia , Gânglio Cervical Superior/patologia , Tálamo/química , Tálamo/embriologia , Tálamo/patologia , Nervo Troclear/química , Nervo Troclear/embriologia , Nervo Troclear/patologiaRESUMO
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.
Assuntos
Nervos Cranianos/química , Nervos Cranianos/citologia , Interneurônios/química , Ácido gama-Aminobutírico/análise , Nervo Abducente/química , Nervo Abducente/citologia , Fatores Etários , Animais , Anticorpos , Lampreias , Larva , Neurônios Motores/química , Nervo Oculomotor/química , Nervo Oculomotor/citologia , Nervo Troclear/química , Nervo Troclear/citologia , Ácido gama-Aminobutírico/imunologiaRESUMO
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.