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Genetic control of wiring specificity in the fly olfactory system - PubMed

Review

Genetic control of wiring specificity in the fly olfactory system

Weizhe Hong et al. Genetics. 2014 Jan.

Abstract

Precise connections established between pre- and postsynaptic partners during development are essential for the proper function of the nervous system. The olfactory system detects a wide variety of odorants and processes the information in a precisely connected neural circuit. A common feature of the olfactory systems from insects to mammals is that the olfactory receptor neurons (ORNs) expressing the same odorant receptor make one-to-one connections with a single class of second-order olfactory projection neurons (PNs). This represents one of the most striking examples of targeting specificity in developmental neurobiology. Recent studies have uncovered central roles of transmembrane and secreted proteins in organizing this one-to-one connection specificity in the olfactory system. Here, we review recent advances in the understanding of how this wiring specificity is genetically controlled and focus on the mechanisms by which transmembrane and secreted proteins regulate different stages of the Drosophila olfactory circuit assembly in a coordinated manner. We also discuss how combinatorial coding, redundancy, and error-correcting ability could contribute to constructing a complex neural circuit in general.

Keywords: Drosophila; cell–cell interaction; olfactory system; transmembrane and secreted proteins; wiring specificity.

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Figures

Figure 1
Figure 1

Organization of the olfactory neural circuit. The olfactory systems from insects to mammals display remarkable similarities with respect to their circuit organization. Individual classes of ORN axons make one-to-one connections with individual classes of second-order PN dendrites within one of ∼50 discrete glomeruli in the antennal lobe. This specific one-to-one connection is referred to as PN–ORN synaptic partner matching. This illustration is modified from Jefferis and Hummel (2006).

Figure 2
Figure 2

Assembly of the Drosophila olfactory circuit. The adult olfactory circuit starts to be assembled at the beginning of the pupal stage. (A) PN dendrite targeting. PNs are born in the embryonic and larval stages and specified by factors involving chromatin remodeling, transcription, microRNA processing, protein translation, glycosylation, and sumoylation. They start to extend their dendrites at the larval–pupal transition, which creates the proto-antennal lobe. Sema-1a cell-autonomously regulates PN dendrite targeting along the dorsolateral–ventromedial axis. Sema-2a/-2b proteins form countergradients to the Sema-1a gradient along the same axis and serve as the extracellular cues that direct this targeting. Subsequently, the differential Caps expression instructs the segregation of PN dendrites into discrete glomeruli. (B) ORN axon targeting. ORNs are born in the early pupa. Pioneering ORN axons arrive at the antennal lobe at 18 hr after puparium formation and choose different trajectories surrounding the antennal lobe. ORN axons require PN-independent mechanisms to converge to appropriate target regions, including ORN–ORN interactions mediated by Sema-1a and ORN target interactions mediated by Hh. By that time, PN dendrites already coarsely pattern the antennal lobe. (C) The independent PN and ORN targeting is coordinated by the one-to-one class-specific matching between ORN axons and PN dendrites. Ten-m and Ten-a, which are highly expressed in select PN and ORN matching pairs, instruct synaptic matching specificity between PNs and ORNs through homophilic attraction.

Figure 3
Figure 3

Discrete expression of Caps instructs PN dendrite targeting into class-specific glomeruli. (A) Schematic showing differential expression of Caps in a subset of PNs that innervate intercalated glomeruli (in gray) in the antennal lobe (e.g., VC1 is Caps+ and DL1 is Caps−). (B) Loss of Caps in VC1 PNs (Caps+) causes their dendrites to invade glomeruli innervated by Caps− PNs. (C) Misexpression of Caps in DL1 PNs (Caps−) causes their dendrites to invade glomeruli innervated by Caps+ PNs. Asterisks indicate the normal and ectopic targets of dendrites. This schematic is from Hong et al. 2009 and de Wit et al. 2011.

Figure 4
Figure 4

Teneurins instruct class-specific matching between PN dendrites and ORN axons. (A) Ten-m and Ten-a are highly expressed in select matching pairs of ORN and PN classes. Shown is a developing antennal lobe at 48 hr after puparium formation stained by antibodies against Ten-m, Ten-a, and a neuropil marker, N-cadherin. Solid lines encircle the DA1 glomerulus (Ten-m low, Ten-a high); dashed lines encircle the VA1d/VA1lm glomeruli (Ten-m high, Ten-a low). (B) High-level expression of Ten-m or Ten-a promotes homophilic attraction between specific pairs of PN dendrites and ORN axons to form proper and stable connections (blue, Ten-m high; orange, Ten-a high). The differential expressions of Ten-m and Ten-a in select PN–ORN pairs instruct the one-to-one class-specific matching. Loss of ten-a in DA1 PNs (Ten-a high) causes dendrites to mismatch with Or47b ORNs (Ten-a low). Misexpression of Ten-m in DA1 PNs (Ten-m low) causes dendrites to mismatch with Or88a and Or47b ORNs (Ten-m high). Misexpression of Ten-a in VA1d PNs (Ten-a low) causes dendrites to mismatch with Or23a and Or67d ORNs (Ten-a high). This schematic is from Hong et al. (2012).

Figure 5
Figure 5

Four hypothetical models of encoding neuronal identities. (A–D) Illustrated are examples of four hypothetical models (illustrated for specific cases in Table 1) by which one molecule or a unique combination of multiple molecules determines the identity of different neuronal classes. (A) Model I. Each class of neurons expresses only one of the molecules. (B–D) Models II–IV. Each class of neurons expresses a unique combination of molecules. (B) Model II. At least one molecule is different between any two classes of neurons. This model has a low robustness. For example, removing molecule C from neuron 3 makes this neuron identical to neuron 9. (C) Model III. At least two molecules are different between any two classes of neurons. Model III has a medium redundancy that increases the robustness of the wiring specificity. For example, removing molecule C from neuron 5 does not make this neuron identical to any other neuronal classes. Removing molecule C from a subset of class 5 neurons may change this subset such that they have the same Hamming distance from the remaining unaltered class 5 neurons as to the classes of neurons that possess the closest identity (i.e., classes with one molecule difference, marked by yellow dots), which could lead to a partial mistargeting. Simultaneous manipulation of two or more molecules (e.g., removing both molecules A and C from neuron 5 or removing C and misexpressing B in neuron 5) may produce stronger phenotypes. If misexpression of a molecule overrides the action of one other molecule, misexpressing molecule C in neuron 4 may cause it to mistarget to places where neurons 1, 2, 6, and 9 are located. (D) Model IV. At least three molecules are different between any two classes of neurons. This model has high redundancy but low coding capacity.

Figure 6
Figure 6

Coding capacity and robustness. (A) Relationship between maximum coding capacity and number of molecules in different models, calculated based on Table 1. The curve of model IV shows the Hamming bound, an upper bound of maximum coding capacity (Table 1). (B and C) Robustness of models II and III, measured by three properties calculated based on Table 2. (B) Percentage of classes unaffected after removal of a given number of molecules. (C) Left, average ectopic targets a class may mistarget following removal of a given number of molecules; right, total mistargeting events following removal of a given number of molecules. The properties in B and C were calculated using representative cases of models II and III in which six and seven molecules are used to encode 64 classes of neurons, respectively. In these two cases, the total numbers of encoded classes are the same, allowing a direct comparison of ectopic targets and mistargeting events between models II and III.

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References

    1. Ang L.-H., Kim J., Stepensky V., Hing H., 2003. Dock and Pak regulate olfactory axon pathfinding in Drosophila. Development 130: 1307–1316. - PubMed
    1. Benton R., Vannice K. S., Gomez-Diaz C., Vosshall L. B., 2009. Variant ionotropic glutamate receptors as chemosensory receptors in Drosophila. Cell 136: 149–162. - PMC - PubMed
    1. Berdnik D., Chihara T., Couto A., Luo L., 2006. Wiring stability of the adult Drosophila olfactory circuit after lesion. J. Neurosci. 26: 3367–3376. - PMC - PubMed
    1. Berdnik D., Fan A. P., Potter C. J., Luo L., 2008. MicroRNA processing pathway regulates olfactory neuron morphogenesis. Curr. Biol. 18: 1754–1759. - PMC - PubMed
    1. Berdnik D., Favaloro V., Luo L., 2012. The SUMO protease Verloren regulates dendrite and axon targeting in olfactory projection neurons. J. Neurosci. 32: 8331–8340. - PMC - PubMed

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