RESUMEN
Dendrites achieve characteristic spacing patterns during development to ensure appropriate coverage of territories. Mechanisms of dendrite positioning via repulsive dendrite-dendrite interactions are beginning to be elucidated, but the control, and importance, of dendrite positioning relative to their substrate is poorly understood. We found that dendritic branches of Drosophila dendritic arborization sensory neurons can be positioned either at the basal surface of epidermal cells, or enclosed within epidermal invaginations. We show that integrins control dendrite positioning on or within the epidermis in a cell autonomous manner by promoting dendritic retention on the basal surface. Loss of integrin function in neurons resulted in excessive self-crossing and dendrite maintenance defects, the former indicating a role for substrate interactions in self-avoidance. In contrast to a contact-mediated mechanism, we find that integrins prevent crossings that are noncontacting between dendrites in different three-dimensional positions, revealing a requirement for combined dendrite-dendrite and dendrite-substrate interactions in self-avoidance.
Asunto(s)
Tipificación del Cuerpo/fisiología , Dendritas/fisiología , Integrinas/metabolismo , Células Receptoras Sensoriales/citología , Animales , Animales Modificados Genéticamente , Tipificación del Cuerpo/genética , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Dendritas/ultraestructura , Drosophila , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Células Epidérmicas , Epidermis/fisiología , Epidermis/ultraestructura , Matriz Extracelular/metabolismo , Regulación del Desarrollo de la Expresión Génica/genética , Proteínas Fluorescentes Verdes/genética , Peroxidasa de Rábano Silvestre/metabolismo , Integrinas/genética , Larva , Microscopía Confocal , Microscopía Electrónica de Transmisión , Modelos Biológicos , Morfogénesis , Órganos de los Sentidos/citología , Células Receptoras Sensoriales/metabolismoRESUMEN
Dendrites distinguish between sister branches and those of other cells. Self-recognition can often lead to repulsion, a process termed "self-avoidance." Here we demonstrate that dendrite self-avoidance in Drosophila da sensory neurons requires cell-recognition molecules encoded by the Dscam locus. By alternative splicing, Dscam encodes a vast number of cell-surface proteins of the immunoglobulin superfamily. We demonstrate that interactions between identical Dscam isoforms on the cell surface underlie self-recognition, while the cytoplasmic tail converts this recognition to dendrite repulsion. Sister dendrites expressing the same isoforms engage in homophilic repulsion. By contrast, Dscam diversity ensures that inappropriate repulsive interactions between dendrites sharing the same receptive field do not occur. The selectivity of Dscam-mediated cell interactions is likely to be widely important in the developing fly nervous system, where processes of cells must distinguish between self and nonself during the construction of neural circuits.