Convergent Local Identity and Topographic Projection of Sensory Neurons

Development of sensory neural circuits requires concurrent specification of neuron modality, position, and topographic projections. However, little is understood about how controls over these distinct parameters can unify in a single developmental sequence. To address this question, we have used the nociceptive class IV dendritic arborization neurons in the Drosophila larval body wall as an excellent model that allows precise spatiotemporal dissection of developmental-genetic control over sensory neuron positioning and wiring, and subsequent analysis of its functional significance for sensorimotor behavior. The class IV neurogenetic program is intrinsic to the anterior domain of the embryonic parasegment epithelium. Along the ventrolateral axis of this domain, nociceptive neuron induction requirements depend upon location. Near the ventral midline, both Hedgehog and Epithelial growth factor receptor signaling are required for class IV neurogenesis. In addition, close to the ventral midline, class IV neurogenesis is preceded by expression of the Iroquois factor Mirror that promotes local nociceptive neuron differentiation. Remarkably, Mirror is also required for the proper routing of class IV topographic axonal projections across the midline of the CNS. Manipulation of Mirror activity in class IV neurons retargeted axonal projections and caused concordant changes in larval nociceptive escape behavior. These findings indicate that convergent sensory neuron specification, local differentiation, and topographic wiring are mediated by Mirror, and they suggest an integrated paradigm for position-sensitive neural development.