Figure 1

Neurons used for studies on neuronal growth at different stages of Drosophila development. (a,c) Horizontal views of a Drosophila larva and adult fly, respectively, illustrating the position of the CNS (grey and cream) in relation to other body structures. (b,d) Three-dimensional extracts from the areas boxed in dark blue in (a,c), respectively. The cell body area of the CNS (cortex (CX)) is shown in light grey, and the neuritic/synaptic area (neuropile (NP)) in cream (only relevant neuropile structures are shown in (b,d)). Black arrows point anterior, morphological structures are annotated in colour code, and neuronal classes are explained in the box at bottom right. The various model neurons are marked with numbers in yellow circles, explained below. Many neurons of the larval trunk can be studied from their birth in the embryo through to the mature synaptic stage. Amongst these, motorneurons (1) project towards the dorsal zone of ipsilateral or ipsi- and contralateral connectives (where they form dendrites; double chevron), from where they enter specific branches of peripheral nerves leading towards their target muscles, on which they form neuromuscular junctions (NMJ; yellow circles represent chemical synapses). Projections of larval interneurons (2) are restricted to the neuropile. Sensory neurons of the trunk (3) project along tracheal branches and motoraxons towards the ventral nerve cord (vNC) where they innervate the ventral domain of connectives [192,195,196,198-200,236]. Sensory neurons in the embryonic trunk have been used, for example, to study the actin-microtubule linker molecule Short stop, signalling through Robo or Notch receptors, or the spatial arrangement of axons in the neuropile [197,202,203,255]. Projections of neurons 1, 2 and 3 in the neuropile of the ventral nerve cord can be classified with respect to their anteroposterior extension within the segment (white curved arrow) or across segments (black curved arrow), their dorsoventral and mediolateral position in connectives (green and red double arrows, respectively), their ipsilateral (neuron 3) versus contralateral (neurons 1 and 2) nature, and their projection through anterior (white arrowhead) versus posterior commissure (black arrowhead; see details in 'Signalling mechanisms involved in axonal pathfinding in Drosophila' above). In the embryonic/larval head region (4), the Bolwig organ has been used for studies of neuronal growth. It contains somata of 12 photoreceptor cells [306], the axons of which form the Bolwig nerve projecting over the antennal and eye discs via the optic stalk into the optic lobe anlage (OLA) [26,307]. The Bolwig nerve is joined by successively outgrowing waves of axons of photoreceptor neurons (5), which are specified in the eye disc during larval and pupal stages. The optic lobe pioneer neuron (6), a projection neuron of embryonic origin, seems to be used as a guide within the OLA by the Bolwig nerve and photoreceptor axons [308,309]. Sensory neurons of the adult trunk (7) develop de novo during larval and pupal stages (with a few exceptions) [310] and terminate in the vNC neuropile (T1-3 and A indicate the three thoracic and fused abdominal segments). They can be analysed from the time of birth through to the fully differentiated stage [311,312], and have been used to study features, such as segment-specific growth regulation (homeotic genes), or the influence of adhesive interactions (Dscam), axonal transport (cut up, the dynein light chain) or of size alterations (gigas) on neuronal growth behaviour [311,313-315]. Photoreceptor cells in the adult compound eye (8) form a precise retinotopic map in the optic lobe (OL: grey 1, lamina; 2, medulla; 3, lobula; 4, lobula plate) established during larval (see neuron 5) and pupal stages, and the genetic mechanisms regulating these precise growth decisions are beginning to be unravelled [316-318]. Interneurons postsynaptic to photoreceptor neurons are well described [317,319] but seem not to have been used for studies of growth mechanisms so far, with the exception of a group of 20–30 dorsal cluster neurons (9; targeted by atoGal4-14A), which form dendrites in the ipsilateral optic lobe and project through the dorsal commissure to innervate the contralateral lobula and medulla [320-322]. Olfactory neurons in the third antennal segment (10) and the maxillary palp (not shown) project from the antenna into the antennal lobe (AL) where they terminate in specific glomeruli in a reproducible pattern correlating with the class of odorant receptor they express; the genetic regulation of this growth behaviour is under investigation [39]. The major output from the AL is constituted by projection neurons (11), which are postsynaptic to olfactory neurons and innervate the lateral horn (red double chevron) and the calyx (blue double chevron), a dorsal structure of the mushroom bodies (MB) [39]. The mushroom bodies are the brain structures responsible for olfactory learning in Drosophila [323,324], and its intrinsic interneurons (Kenyon cells (12)) project through the calyx and pedunculus where many of them bifurcate to project into the vertical α/α'-and the horizontal β/β'/γ-lobes, simultaneously [325]. The large giant fibre neuron (13) connects the optic system via a large diameter axon with motorneurons in the second thoracic segment (14), innervating the tergotrochanteral muscle (TTM; responsible for the visually induced jump escape response) via chemical and electrical (orange triangle) synapses [326]. Giant fibre axons grow out during late larval/pupal stages and have been used to study growth regulatory mechanism, such as the influence of Rho-like GTPases or the role of the E2 ubiquitin ligase Bendless [326]. Ocellar photoreceptor neurons do not send out their own axons but are connected to the brain via large interneurons, the cell bodies of which are located in the brain originally, but migrate into the periphery during pupal development (15). The pathfinding of these interneurons depends on a set of short-lived pioneer neurons that, in turn, require the extracellular matrix molecule laminin, the transmembrane receptor neurotactin and its ligand Amalgam for proper outgrowth [21,239,241]. Further potentially attractive models for studies of neuronal growth that are not shown here are auditory sensory neurons [327], and axonal fascicles in the ventral nerve cord of late Drosophila larvae representing paused interneurons of the future adult CNS (not shown) [209].