RESUMEN

Connexins are transmembrane proteins forming gap junction channels for direct intercellular and, for example in myelinating glia cells, intracellular communication. In mature myelin-forming Schwann cells, expression of multiple connexins, i.e. connexin (Cx) 43, Cx29, Cx32, and Cx46 (after nerve injury) has been detected. However, little is known about connexin protein expression during Schwann cell development. Here we use histochemical methods on wildtype and Cx29lacZ transgenic mice to investigate the developmental expression of connexins in the Schwann cell lineage. Our data demonstrate that in the mouse Cx43, Cx29, and Cx32 protein expression is activated in a developmental sequence that is clearly correlated with major developmental steps in the lineage. Only Cx43 was expressed from neural crest cells onwards. Cx29 protein expression was absent from neural crest cells but appeared as neural crest cells generated precursors (embryonic day 12) both in vivo and in vitro. This identifies Cx29 as a novel marker for cells of the defined Schwann cell lineage. The only exception to this were dorsal roots, where the expression of Cx29 was delayed four days relative to ventral roots and spinal nerves. Expression of Cx32 commenced postnatally, coinciding with the onset of myelination. Thus, the coordinated expression of connexin proteins in cells of the embryonic and postnatal Schwann cell lineage might point to a potential role in peripheral nerve development and maturation.

Asunto(s)

Diferenciación Celular/fisiología , Conexinas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Cresta Neural/metabolismo , Sistema Nervioso Periférico/embriología , Sistema Nervioso Periférico/crecimiento & desarrollo , Células de Schwann/metabolismo , Células Madre/metabolismo , Animales , Animales Recién Nacidos , Biomarcadores , Linaje de la Célula/fisiología , Células Cultivadas , Conexina 43 , Conexinas/genética , Femenino , Uniones Comunicantes/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas del Tejido Nervioso/genética , Cresta Neural/citología , Sistema Nervioso Periférico/citología , Células de Schwann/citología , Raíces Nerviosas Espinales/citología , Raíces Nerviosas Espinales/embriología , Raíces Nerviosas Espinales/metabolismo , Células Madre/citología , Proteína beta1 de Unión Comunicante

RESUMEN

Using newly generated transgenic mice in which the coding region of the connexin29 (Cx29) gene was replaced by the lacZ reporter gene, we confirmed previous immunochemical results that Cx29 is expressed in Schwann cells, oligodendrocytes and Bergmann glia cells. In addition, we detected lacZ/Cx29 in Schwann cells of the sciatic nerve and in particular of the spiral ganglion in the inner ear, as well as at low abundance in the stria vascularis. Furthermore, we found lacZ/Cx29 expression in nonmyelinating Schwann cells of the adrenal gland, in chondrocytes of intervertebral discs and the epiphysis of developing bones. Electron microscopic analyses of myelin sheaths in the central and peripheral nervous system of Cx29-deficient mice detected no abnormalities. The nerve conduction in the sciatic nerve of adult Cx29-deficient mice and the auditory brain stem response as well as visually evoked potentials in 4- to 10-week-old Cx29-deficient mice were not different from wild-type littermate controls. Thus, in contrast to connexin32 and connexin47, which are also expressed in myelinating cells, Cx29 does not contribute to the function of myelin in adult mice.

Asunto(s)

Médula Suprarrenal/metabolismo , Huesos/metabolismo , Cartílago/metabolismo , Conexinas/biosíntesis , Conexinas/genética , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Sistema Nervioso/metabolismo , Médula Suprarrenal/citología , Animales , Cartílago/citología , Condrocitos/metabolismo , Epífisis/metabolismo , Potenciales Evocados Auditivos del Tronco Encefálico/genética , Potenciales Evocados Visuales/genética , Femenino , Genes Reporteros , Operón Lac , Masculino , Ratones , Ratones Transgénicos , Microscopía Electrónica de Transmisión , Vaina de Mielina/metabolismo , Vaina de Mielina/ultraestructura , Sistema Nervioso/citología , Conducción Nerviosa/genética , Células de Schwann/metabolismo , Células de Schwann/ultraestructura , Nervio Ciático/citología , Nervio Ciático/metabolismo , Ganglio Espiral de la Cóclea/citología , Ganglio Espiral de la Cóclea/metabolismo

RESUMEN

Recent research results indicate that glial gap-junction communication is much more complex and widespread than originally thought, and has diverse roles in brain homeostasis and the response of the brain to injury. The situation is far from clear, however. Pharmacological agents that block gap junctions can abolish neuron-glia long-range signaling and can alleviate neuronal damage whereas, intriguingly, opposite effects are observed in mice lacking connexin43, a major gap-junction subunit protein in astrocytes. How can the apparently contradictory results be explained, and how is specificity achieved within the glial gap-junction system? Another key issue in understanding glial connexin function is that oligodendrocytes and astrocytes, each of which express distinct connexin isotypes, are thought to participate in brain homeostasis by forming a panglial syncytium. Molecular analysis has revealed a surprising diversity of connexin expression and function, and this has led to new hypotheses regarding their roles in the brain, which could be tested using new approaches.

Asunto(s)

Encéfalo/citología , Comunicación Celular/fisiología , Conexinas/fisiología , Neuroglía/fisiología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Conexinas/aislamiento & purificación , Uniones Comunicantes/efectos de los fármacos , Uniones Comunicantes/fisiología , Regulación de la Expresión Génica/fisiología , Humanos , Modelos Neurológicos , Neuroglía/clasificación , Neuronas/fisiología , Transmisión Sináptica

RESUMEN

In this study we show by Northern blot hybridization that the novel human (h) connexin (Cx) genes hCx25, hCx30.2, hCx31.9, hCx40.1, hCx59, and hCx62 are transcribed in different adult tissues. The hCx25 RNA is slightly expressed in placenta, and hCx59 and hCx62 RNA are both transcribed in skeletal muscle, although the latter is also slightly expressed in heart. Expression profiles of three orthologous human (h) and mouse (m) connexin gene pairs, i.e., hCx30.2 versus mCx29, hCx40.1 versus mCx39, and hCx62 versus mCx57, differ strongly, in contrast to other orthologous connexins with higher sequence identities. Thus, several of the new human connexin genes appear to have evolved to different expression patterns and presumably to different functions compared to their orthologues in the mouse genome. (121)

Asunto(s)

Conexinas/biosíntesis , Animales , Secuencia de Bases , Northern Blotting , Clonación Molecular , Conexinas/química , Exones , Humanos , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Músculo Esquelético/metabolismo , Miocardio/metabolismo , Placenta/metabolismo , Reacción en Cadena de la Polimerasa , ARN/química , ARN Mensajero/metabolismo , Homología de Secuencia de Ácido Nucleico , Distribución Tisular , Transcripción Genética

RESUMEN

Gap junctions are clustered channels between contacting cells through which direct intercellular communication via diffusion of ions and metabolites can occur. Two hemichannels, each built up of six connexin protein subunits in the plasma membrane of adjacent cells, can dock to each other to form conduits between cells. We have recently screened mouse and human genomic data bases and have found 19 connexin (Cx) genes in the mouse genome and 20 connexin genes in the human genome. One mouse connexin gene and two human connexin genes do not appear to have orthologs in the other genome. With three exceptions, the characterized connexin genes comprise two exons whereby the complete reading frame is located on the second exon. Targeted ablation of eleven mouse connexin genes revealed basic insights into the functional diversity of the connexin gene family. In addition, the phenotypes of human genetic disorders caused by mutated connexin genes further complement our understanding of connexin functions in the human organism. In this review we compare currently identified connexin genes in both the mouse and human genome and discuss the functions of gap junctions deduced from targeted mouse mutants and human genetic disorders.

Asunto(s)

Conexinas/genética , Uniones Comunicantes/fisiología , Empalme Alternativo , Animales , Conexinas/fisiología , Mutación del Sistema de Lectura , Expresión Génica , Marcación de Gen , Enfermedades Genéticas Congénitas/genética , Genoma Humano , Humanos , Ratones , Ratones Transgénicos