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1.  Regulation of locomotion and motoneuron trajectory selection and targeting by the Drosophila homolog of Olig family transcription factors 
Developmental Biology  2012;369(2-2):261-276.
During the development of locomotion circuits it is essential that motoneurons with distinct subtype identities select the correct trajectories and target muscles. In vertebrates, the generation of motoneurons and myelinating glia depends on Olig2, one of the five Olig family bHLH transcription factors. We investigated the so far unknown function of the single Drosophila homolog Oli. Combining behavioral and genetic approaches, we demonstrate that oli is not required for gliogenesis, but plays pivotal roles in regulating larval and adult locomotion, and axon pathfinding and targeting of embryonic motoneurons. In the embryonic nervous system, Oli is primarily expressed in postmitotic progeny, and in particular, in distinct ventral motoneuron subtypes. oli mediates axonal trajectory selection of these motoneurons within the ventral nerve cord and targeting to specific muscles. Genetic interaction assays suggest that oli acts as part of a conserved transcription factor ensemble including Lim3, Islet and Hb9. Moreover, oli is expressed in postembryonic leg-innervating motoneuron lineages and required in glutamatergic neurons for walking. Finally, over-expression of vertebrate Olig2 partially rescues the walking defects of oli-deficient flies. Thus, our findings reveal a remarkably conserved role of Drosophila Oli and vertebrate family members in regulating motoneuron development, while the steps that require their function differ in detail.
► Drosophila Oli is expressed in embryonic ventral motoneuron subtypes. ► oli controls axonal trajectory selection and muscle targeting during embryogenesis. ► Oli acts as part of a conserved transcription factor ensemble that includes Hb9. ► Oli is expressed in postembryonic leg-innervating motoneuron lineages. ► Oli is required in glutamatergic neurons for adult locomotion.
PMCID: PMC3464432  PMID: 22796650
bHLH transcription factor; Neuron specification; Glial development; Motoneurons; Locomotion
2.  Localized Netrins Act as Positional Cues to Control Layer-Specific Targeting of Photoreceptor Axons in Drosophila 
Neuron  2012;75(1):80-93.
A shared feature of many neural circuits is their organization into synaptic layers. However, the mechanisms that direct neurites to distinct layers remain poorly understood. We identified a central role for Netrins and their receptor Frazzled in mediating layer-specific axon targeting in the Drosophila visual system. Frazzled is expressed and cell autonomously required in R8 photoreceptors for directing their axons to the medulla-neuropil layer M3. Netrin-B is specifically localized in this layer owing to axonal release by lamina neurons L3 and capture by target neuron-associated Frazzled. Ligand expression in L3 is sufficient to rescue R8 axon-targeting defects of Netrin mutants. R8 axons target normally despite replacement of diffusible Netrin-B by membrane-tethered ligands. Finally, Netrin localization is instructive because expression in ectopic layers can retarget R8 axons. We propose that provision of localized chemoattractants by intermediate target neurons represents a highly precise strategy to direct axons to a positionally defined layer.
► Netrins selectively target Frazzled-expressing R8 photoreceptor axons to layer M3 ► Precise positional information is generated by Netrin localization in a single layer ► Local axonal release and receptor-mediated capture restrict ligand distribution ► Layer-specific targeting relies on ligand release by intermediate target neurons
Many neural circuits share a remarkable organization into synaptic layers. Timofeev et al. find that in the Drosophila visual system, Netrins act as short-range chemoattractants to target photoreceptor axons, specifically expressing the Frazzled/DCC/Unc-40 receptor, to a single positionally defined layer.
PMCID: PMC3398394  PMID: 22794263
3.  Glial cell development and function in the Drosophila visual system 
Neuron glia biology  2007;3(1):17-25.
In the developing nervous system, building a functional neuronal network relies on coordinating the formation, specification and survival to diverse neuronal and glial cell subtypes. The establishment of neuronal connections further depends on sequential neuron–neuron and neuron–glia interactions that regulate cell-migration patterns and axon guidance. The visual system of Drosophila has a highly regular, retinotopic organization into reiterated interconnected synaptic circuits. It is therefore an excellent invertebrate model to investigate basic cellular strategies and molecular determinants regulating the different developmental processes that lead to network formation. Studies in the visual system have provided important insights into the mechanisms by which photoreceptor axons connect with their synaptic partners within the optic lobe. In this review, we highlight that this system is also well suited for uncovering general principles that underlie glial cell biology. We describe the glial cell subtypes in the visual system and discuss recent findings about their development and migration. Finally, we outline the pivotal roles of glial cells in mediating neural circuit assembly, boundary formation, neural proliferation and survival, as well as synaptic function.
PMCID: PMC2265801  PMID: 18333286
Optic lobe; photoreceptor axons; axon guidance; migration; neurogenesis

Results 1-3 (3)