RESUMEN
The spatiotemporal integration of adhesion and signaling during neuritogenesis is an important prerequisite for the establishment of neuronal networks in the developing brain. In this study, we describe the role of the L1-type CAM Neuroglian protein (NRG) in different steps of Drosophila mushroom body (MB) neuron axonogenesis. Selective axon bundling in the peduncle requires both the extracellular and the intracellular domain of NRG. We uncover a novel role for the ZO-1 homolog Polychaetoid (PYD) in axon branching and in sister branch outgrowth and guidance downstream of the neuron-specific isoform NRG-180. Furthermore, genetic analyses show that the role of NRG in different aspects of MB axonal development not only involves PYD, but also TRIO, SEMA-1A and RAC1.
Asunto(s)
Axones/metabolismo , Moléculas de Adhesión Celular Neuronal/metabolismo , Proteínas de Drosophila/metabolismo , Cuerpos Pedunculados/citología , Cuerpos Pedunculados/metabolismo , Molécula L1 de Adhesión de Célula Nerviosa/metabolismo , Animales , Axones/fisiología , Moléculas de Adhesión Celular Neuronal/genética , Línea Celular , Drosophila , Proteínas de Drosophila/genética , Femenino , Inmunohistoquímica , Masculino , Molécula L1 de Adhesión de Célula Nerviosa/genética , Organogénesis/genética , Organogénesis/fisiología , Reacción en Cadena de la Polimerasa , Transducción de Señal/genética , Transducción de Señal/fisiologíaRESUMEN
Correct wiring of the mushroom body (MB) neuropil in the Drosophila brain involves appropriate positioning of different axonal lobes, as well as the sister branches that develop from individual axons. This positioning requires the integration of various guidance cues provided by different cell types, which help the axons find their final positions within the neuropil. Semaphorins are well-known for their conserved roles in neuronal development and axon guidance. We investigated the role of Sema-1a in MB development more closely. We show that Sema-1a is expressed in the MBs as well as surrounding structures, including the glial transient interhemispheric fibrous ring, throughout development. By loss- and gain-of-function experiments, we show that the MB axons display lobe and sister branch-specific Sema-1a signaling, which controls different aspects of axon outgrowth and guidance. Furthermore, we demonstrate that these effects are modulated by the integration of MB intrinsic and extrinsic Sema-1a signaling pathways involving PlexA and PlexB. Finally, we also show a role for neuronal- glial interaction in Sema-1a dependent ß-lobe outgrowth.