RESUMEN
How action potentials regulate myelination by oligodendrocytes is uncertain. We show that neuronal activity raises [Ca2+]i in developing oligodendrocytes in vivo and that myelin sheath elongation is promoted by a high frequency of [Ca2+]i transients and prevented by [Ca2+]i buffering. Sheath elongation occurs ~1 h after [Ca2+]i elevation. Sheath shortening is associated with a low frequency of [Ca2+]i transients but with longer duration [Ca2+]i bursts. Thus, [Ca2+]i controls myelin sheath development.
Asunto(s)
Axones/fisiología , Calcio/metabolismo , Vaina de Mielina/fisiología , Neuronas/fisiología , Oligodendroglía/fisiología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/genética , Animales , Animales Modificados Genéticamente , Axones/efectos de los fármacos , Calcio/farmacología , Quelantes/farmacología , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Ácido Egtácico/análogos & derivados , Ácido Egtácico/farmacología , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Mivacurio/farmacología , Proteína Básica de Mielina/genética , Proteína Básica de Mielina/metabolismo , Fármacos Neuromusculares no Despolarizantes/farmacología , Neuronas/efectos de los fármacos , Factores de Transcripción SOXE/genética , Factores de Transcripción SOXE/metabolismo , Bloqueadores de los Canales de Sodio/farmacología , Médula Espinal/citología , Tetrodotoxina/farmacología , Pez Cebra , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
The role of NMDA receptors in oligodendrocytes has been controversial. A new paper (Saab et al., 2016) suggests they play a key role in regulating glucose uptake in response to axonal glutamate release, thus controlling metabolic cooperation between oligodendrocytes and axons.
Asunto(s)
Axones/metabolismo , Calcio/metabolismo , Neuronas/metabolismo , Oligodendroglía/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animales , Ácido Glutámico/metabolismo , HumanosRESUMEN
Maintaining neurogenesis in growing tissues requires a tight balance between progenitor cell proliferation and differentiation. In the zebrafish retina, neuronal differentiation proceeds in two stages with embryonic retinal progenitor cells (RPCs) of the central retina accounting for the first rounds of differentiation, and stem cells from the ciliary marginal zone (CMZ) being responsible for late neurogenesis and growth of the eye. In this study, we analyse two mutants with small eyes that display defects during both early and late phases of retinal neurogenesis. These mutants carry lesions in gdf6a, a gene encoding a BMP family member previously implicated in dorsoventral patterning of the eye. We show that gdf6a mutant eyes exhibit expanded retinoic acid (RA) signalling and demonstrate that exogenous activation of this pathway in wild-type eyes inhibits retinal growth, generating small eyes with a reduced CMZ and fewer proliferating progenitors, similar to gdf6a mutants. We provide evidence that RA regulates the timing of RPC differentiation by promoting cell cycle exit. Furthermore, reducing RA signalling in gdf6a mutants re-establishes appropriate timing of embryonic retinal neurogenesis and restores putative stem and progenitor cell populations in the CMZ. Together, our results support a model in which dorsally expressed gdf6a limits RA pathway activity to control the transition from proliferation to differentiation in the growing eye.