Neural maps are emergent, highly ordered structures that are essential for organizing and presenting synaptic information. position the termini of axons (sites of synaptic output), independent of their synaptic partners. We suggest that the coordinated targeting of both input and output elements of a neural system into a common space using shared global guidance cues could be a simple way of establishing the specificity of synaptic connections within neural networks. Introduction The fidelity with which connections are made between neurons is a striking feature of nervous system design and essential for proper function [1]. How appropriate presynaptic and postsynaptic elements are brought together 476-32-4 supplier during development to generate such ordered connectivity is still a major unanswered question in neurobiology [2]. Most developmental studies investigating the generation of neural maps [3] or synaptic laminae EPHB2 [4] have focussed around the role that presynaptic elements play in establishing normal connectivity and the mechanisms that guide axons [5]. This axonocentric bias is understandable as the orderly growth of axons to their targets often reveals an explicit anatomical framework, upon which one can ask questions about mechanisms of network formation [6]. The role that dendrites, the major postsynaptic elements, play in the development of connectivity has been much less explored [7]. Dendrite shape is known to have important implications for neuron function as it determines a cell’s integrative properties [8] and dictates the synaptic inputs it will receive [9],[10]. Thus cell-type-specific programs of dendrite development ultimately have a profound effect on the role a cell plays within a network [11]. Two very different modes of growth can generate a dendritic tree of the same basic shape: neurons can either profusely elaborate dendrites across a wide field and then selectively remove branches from inappropriate territories, or alternatively, dendrite growth can be targeted into distinct territories using guidance mechanisms similar to those found in axons [12]. Examples of both types of growth have been observed. The first mode of growth is seen in mammalian retinal ganglion cells to generate ON and OFF sub-laminae of the Inner Plexiform 476-32-4 supplier Layer [13]. The second mode of growth, dendritic targeting, is seen in the generation of both neural maps and synaptic laminae. In generate a dendritic map within the CNS that represents the innervation of body wall muscles [18]. These central projections are highly ordered and likely reflect some underlying organization of pre-motor interneurons within the 476-32-4 supplier network. The map develops in the absence of target muscles, glial cells, or competitive interactions with adjacent dendrites, suggesting that coordinated cell-intrinsic programs for targeting are likely to be important for its assembly [18]. Although our understanding of the molecular mechanisms that control dendritogenesis is still incomplete, a number of transcription factors have been identified that coordinate the patterning of dendritic maps [19],[20],[21]. At present however the only downstream effector molecule known to be required for dendritic map development is Semaphorin-1a. Both loss- and gain-of-function experiments demonstrate that this levels of Semaphorin-1a, acting cell-autonomously as a receptor or a part of a receptor complex, direct the dendritic targeting of projection neurons along the dorsolateral to ventromedial axis of the antennal lobe during map formation [22]. Here we investigate how the dendrites of leg motoneurons are targeted to distinct neuropil territories and how these mechanisms can collectively generate a neural map. The majority of leg motoneurons are born during larval life and the bulk of those are derived from a single neuroblast lineage, lineage 15 [23, unpublished data]. The neurons of lineage 15 form stereotyped projection patterns, dependent on their birth-order within the lineage. Early-born cells innervate proximal muscle targets and elaborate dendrites from medial to lateral territories, whereas late-born cells innervate more distal muscle groups within the leg and establish dendritic arborizations that are largely confined to lateral territories in the neuropil. Here we show how two subtypes, within this lineage, generate their distinct dendritic arborizations by targeting growth into specific territories using the midline signalling systems of Slit-Robo and Netrin-Fra. These data suggest that cell intrinsic blends of guidance molecules marshal the dendrites of this lineage into appropriate territories in a coordinated fashion to generate a.