RESUMO
Contactin1a (Cntn1a) is a zebrafish homolog of contactin1 (F3/F11/contactin) in mammals, an immunoglobulin superfamily recognition molecule of neurons and oligodendrocytes. We describe conspicuous Cntn1a mRNA expression in oligodendrocytes in the developing optic pathway of zebrafish. In adults, this expression is only retained in glial cells in the intraretinal optic fiber layer, which contains 'loose' myelin. After optic nerve lesion, oligodendrocytes re-express Cntn1a mRNA independently of the presence of regenerating axons and retinal ganglion cells upregulate Cntn1a expression to levels that are significantly higher than those during development. After spinal cord lesion, expression of Cntn1a mRNA is similarly increased in axotomized brainstem neurons and white matter glial cells in the spinal cord. In addition, reduced mRNA expression in the trigeminal/anterior lateral line ganglion in erbb3-deficient mutant larvae implies Cntn1a in Schwann cell differentiation. These complex regulation patterns suggest roles for Cntn1a in myelinating cells and neurons particularly in successful CNS regeneration.
Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Diferenciação Celular/fisiologia , Sistema Nervoso Central/patologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Regeneração Nervosa/fisiologia , Oligodendroglia/fisiologia , Animais , Animais Geneticamente Modificados , Animais Recém-Nascidos , Moléculas de Adesão Celular Neuronais/genética , Sistema Nervoso Central/fisiopatologia , Contactina 1 , Contactinas , Embrião não Mamífero , Enucleação Ocular/métodos , Hibridização In Situ/métodos , Microscopia Eletrônica de Transmissão/métodos , Proteína P0 da Mielina/metabolismo , Glicoproteína Associada a Mielina/metabolismo , Neurônios/fisiologia , Neurônios/ultraestrutura , Oligodendroglia/ultraestrutura , Traumatismos do Nervo Óptico/patologia , Traumatismos do Nervo Óptico/fisiopatologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor ErbB-3/genética , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Peixe-Zebra , Proteínas de Peixe-ZebraRESUMO
We have identified a zebrafish homolog of the F3/F11/contactin (F3) recognition molecule. The gene shares 55% amino acid identity with F3 molecules in other vertebrates. Expression of F3 mRNA is first detectable at 16 h post-fertilization (hpf) in trigeminal and Rohon-Beard neurons. At 18-24 hpf, additional weaker expression is present in discrete cell clusters in the hindbrain, in the anterior lateral line/acoustic ganglion and in spinal motor neurons. Transcription factors of the LIM homeodomain class (LIM-HD) and their associated cofactors CLIM/NLI/Ldb (CLIM) have been implicated in the development of peripheral axons of trigeminal and Rohon-Beard neurons. We demonstrate that ectopic overexpression of a dominant-negative CLIM molecule early during zebrafish development strongly reduces expression of F3 mRNA in these neurons indicating regulation of F3 by the LIM-HD protein network. These results and the spatiotemporal correlation of F3 expression with axonal differentiation in a subset of primary neurons suggest an important role of F3 for axon growth.
Assuntos
Moléculas de Adesão Celular Neuronais/genética , Diferenciação Celular/fisiologia , Neurônios/metabolismo , Peixe-Zebra/genética , Sequência de Aminoácidos , Animais , Moléculas de Adesão Celular Neuronais/biossíntese , Contactinas , Hibridização In Situ , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Fatores de Transcrição/metabolismo , Gânglio Trigeminal/metabolismo , Peixe-Zebra/embriologiaRESUMO
We have identified a zebrafish homolog of the F3/F11/contactin (F3) recognition molecule. The gene shares 55% amino acid identity with F3 molecules in other vertebrates. Expression of F3 mRNA is first detectable at 16 h post-fertilization (hpf) in trigeminal and Rohon-Beard neurons. At 18-24 hpf, additional weaker expression is present in discrete cell clusters in the hindbrain, in the anterior lateral line/acoustic ganglion and in spinal motor neurons. Transcription factors of the LIM homeodomain class (LIM-HD) and their associated cofactors CLIM/NLI/Ldb (CLIM) have been implicated in the development of peripheral axons of trigeminal and Rohon-Beard neurons. We demonstrate that ectopic overexpression of a dominant-negative CLIM molecule early during zebrafish development strongly reduces expression of F3 mRNA in these neurons indicating regulation of F3 by the LIM-HD protein network. These results and the spatiotemporal correlation of F3 expression with axonal differentiation in a subset of primary neurons suggest an important role of F3 for axon growth.
