1. Assembly of the fly olfactory circuit
The central problem of neural circuit assembly is how wiring specificity is achieved. The assembly of the fly olfactory system requires precise glomerular targeting of axons from each of the 50 olfactory receptor neuron types and dendrites from each of the 50 projection neuron types (Fig. 1). We have used this neural circuit to investigate the general principles by which wiring specificity is established during development (e.g., Fig. 2). Our studies have made the fly olfactory circuit one of the best understood in cellular and molecular mechanisms of circuit assembly. These investigations have also identified wiring specificity molecules for us to examine their homologs in circuit assembly in the more complex mammalian brain (see Section 2 ). |
|Fig. 1: Drosophila olfactory circuit. Olfactory receptor neurons (ORNs) expressing the same receptor (same color) target their axons to the same glomerulus in the antennal lobe. Projection neuron (PN) dendrites also target to single glomerulus, and their axons project to the mushroom body and lateral horn that mediate learned and innate olfactory behavior. A single PN is labeled here using the MARCM method. In the wiring of the fly olfactory circuit, 50 types of ORNs form precise, one-to-one connection with 50 types of PNs. |
|Fig. 2: Teneurins instruct synaptic partner matching. (A) Expression pattern of Ten-m (green) and Ten-a (red) in the developing antennal lobe, with magenta neuropil marker labeling all glomeruli evenly. The solid circles highlight the DA1 glomerulus, which has a high level of Ten-a and a low level of Ten-m. The dashed circles highlight the VA1d and VA1v glomeruli, which have a high level of Ten-m and low level of Ten-a. (B) Schematic summary of matching Teneurin expression in five glomeruli. PNs and ORNs target the same glomerulus exhibit matching level of Ten-m (blue) and Ten-a (orange) expression. Double arrows symbolize the hypothesis that the matching levels of Teneurins instruct synaptic partner matching between cognate ORNs and PNs. After Hong W, Mosca TJ & Luo L (2012) Nature 484:201-207.|
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Komiyama T*, Johnson WA, Luo L & Jefferis GSXE* (2003) From lineage to wiring specificity: POU domain transcription factors control precise connections of Drosophila olfactory projection neurons. Cell 112:157-167.
Jefferis GSXE, Vyas, RM, Berdnik D, Ramaekers A, Stocker RF, Tanaka N, Ito K & Luo L (2003) Developmental origin of wiring specificity in the olfactory system of Drosophila. Development 131: 117-130.
Zhu H, Hummel T, Clemens JC, Berdnik D, Zipursky SL & Luo L (2006) Dendritic patterning by Dscam and synaptic partner matching in the Drosophila antennal lobe. Nat Neurosci 9: 349-55.
Komiyama T, Sweeney LB, Schuldiner O, Garcia KC & Luo L (2007) Graded expression of Semephorin-1a cell-autonomously directs dendritic targeting of olfactory projection neurons. Cell 128: 399-410.
Hong W, Zhu H, Potter CJ, Barsh G, Kurusu M, Zinn K & Luo L (2009) Leucine-rich repeat transmembrane proteins instruct discrete dendrite targeting in an olfactory map. Nat Neurosci 12: 1542-1550.
Chou YH, Zheng X, Beachy PA & Luo L (2010) Patterning axon targeting of olfactory receptor neurons by coupled Hedgehog signaling at two distinct steps. Cell 142: 954-966.
Sweeney LB, Chou YH, Wu Z, Joo W, Komiyama T, Potter CJ, Kolodkin AL, Garcia KC & Luo L (2011) Secreted semaphorins from degenerating larval ORN axons direct adult projection neuron dendrite targeting. Neuron 72: 734-47.
Hong W, Mosca TJ & Luo L (2012) Teneurins instruct synaptic partner matching in an olfactory map. Nature 484: 201-207.
Joo WJ, Sweeney LB, Liang L & Luo L (2013) Linking cell fate, trajectory choice, and target selection: genetic analysis of sema-2b in olfactory axon targeting. Neuron 78:673-86.
Mosca TJ & Luo L (2014). Synaptic organization of the Drosophila antennal lobe and its regulation by the Teneurins. eLife 3:e03726.
Ward A, Hong W, Favaloro V & Luo L (2015). Toll receptors instruct axon and dendrite targeting and participate in synaptic partner matching in a Drosophila olfactory circuit. Neuron 85:1013-1028.
Wu B, Li J, Chou YH, Luginbuhl D & Luo L (2017) Fibroblast growth factor signaling instructs ensheathing glia wrapping of Drosophila olfactory glomeruli. Proc Natl Acad Sci USA 114:7505-7512.
Li H*, Horns F*, Wu B, Xie Q, Li J, Li T, Luginbuhl DJ, Quake SR & Luo L (2017) Classifying Drosophila olfactory projection neuron subtypes by single-cell RNA sequencing. Cell 171:1206-1220.
Li J, Guajardo R, Xu C, Wu B, Li H, Li T, Luginbuhl D, Xie X & Luo L (2018) Stepwise wiring of the Drosophila olfactory map requires specific Plexin B levels. eLife 7:e39088.
* co-first authors.
See publications for complete list and PDFs.