RESUMEN
Sensory neurons with common functions are often nonrandomly arranged and form dendritic territories in stereotypic spatial patterns throughout the nervous system, yet molecular mechanisms of how neurons specify dendritic territories remain largely unknown. In Drosophila larvae, dendrites of class IV sensory (C4da) neurons completely but nonredundantly cover the whole epidermis, and the boundaries of these tiled dendritic fields are specified through repulsive interactions between homotypic dendrites. Here we report that, unlike the larval C4da neurons, adult C4da neurons rely on both dendritic repulsive interactions and external positional cues to delimit the boundaries of their dendritic fields. We identify Wnt5 derived from sternites, the ventral-most part of the adult abdominal epidermis, as the critical determinant for the ventral boundaries. Further genetic data indicate that Wnt5 promotes dendrite termination on the periphery of sternites through the Ryk receptor family kinase Derailed (Drl) and the Rho GTPase guanine nucleotide exchange factor Trio in C4da neurons. Our findings thus uncover the dendritic contact-independent mechanism that is required for dendritic boundary specification and suggest that combinatory actions of the dendritic contact-dependent and -independent mechanisms may ensure appropriate dendritic territories of a given neuron.
Asunto(s)
Dendritas , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citología , Drosophila melanogaster/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Células Receptoras Sensoriales , Transducción de Señal , Proteínas Wnt/metabolismo , Animales , Dendritas/genética , Dendritas/metabolismo , Drosophila melanogaster/enzimología , Drosophila melanogaster/genética , Células Epidérmicas , Epidermis/metabolismo , Factores de Intercambio de Guanina Nucleótido/metabolismo , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Células Receptoras Sensoriales/citología , Células Receptoras Sensoriales/metabolismoRESUMEN
The refinement of neural circuits involves dendrite pruning, a process that removes inappropriate projections that are formed during development. In Drosophila sensory neurons, compartmentalized calcium (Ca(2+)) transients in dendrites act as spatiotemporal cues to trigger pruning, yet how neurons define the dendrites with Ca(2+) transients remains elusive. Here we report that local elevation of endocytic activity contributes to defining dendrites that generate Ca(2+) transients, triggering pruning. In vivo imaging of single dendrites reveals an increase of endocytosis in proximal dendrites that spatially and temporally correlates with dendrite thinning, an early step in pruning tightly coupled with compartmentalized Ca(2+) transients. Two GTPases, Rab5 and dynamin, are required for both the increased endocytic activity and compartmentalized Ca(2+) transients. Further genetic analyses suggest that local endocytosis in proximal dendrites functions cooperatively with global endocytosis-mediated protein degradation pathways to promote dendrite pruning.
Asunto(s)
Dendritas/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Dinaminas/genética , Endocitosis/genética , Plasticidad Neuronal/genética , Proteínas de Unión al GTP rab5/genética , Animales , Animales Modificados Genéticamente , Calcio/metabolismo , Señalización del Calcio , Compartimento Celular , Dendritas/ultraestructura , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/metabolismo , Dinaminas/metabolismo , Endosomas/metabolismo , Regulación del Desarrollo de la Expresión Génica , Metamorfosis Biológica/genética , Imagen Molecular , Proteolisis , Células Receptoras Sensoriales/metabolismo , Células Receptoras Sensoriales/ultraestructura , Proteínas de Unión al GTP rab5/metabolismoRESUMEN
Dendrite pruning is critical for sculpting the final connectivity of neural circuits as it removes inappropriate projections, yet how neurons can selectively eliminate unnecessary dendritic branches remains elusive. Here, we show that calcium transients that are compartmentalized in specific dendritic branches act as temporal and spatial cues to trigger pruning in Drosophila sensory neurons. Calcium transients occurred in local dendrites at ~3 hours before branch elimination. In dendritic branches, intrinsic excitability increased locally to activate calcium influx via the voltage-gated calcium channels (VGCCs), and blockade of the VGCC activities impaired pruning. Further genetic analyses suggest that the calcium-activated protease calpain functions downstream of the calcium transients. Our findings reveal the importance of the compartmentalized subdendritic calcium signaling in spatiotemporally selective elimination of dendritic branches.
Asunto(s)
Calcio/metabolismo , Dendritas/fisiología , Células Receptoras Sensoriales/fisiología , Animales , Canales de Calcio/metabolismo , Señalización del Calcio , Calpaína/genética , Calpaína/metabolismo , Dendritas/ultraestructura , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Femenino , Masculino , Metamorfosis BiológicaRESUMEN
The brain changes in response to experience and altered environment. To do that, the nervous system often remodels the structures of neuronal circuits. This structural plasticity of the neuronal circuits appears to be controlled not only by intrinsic factors, but also by extrinsic mechanisms including modification of the extracellular matrix. Recent studies employing a range of animal models implicate that matrix metalloproteinases regulate multiple aspects of the neuronal development and remodeling in the brain. This paper aims to summarize recent advances of our knowledge on the neuronal functions of matrix metalloproteinases and discuss how they might relate in neuronal disease.