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Teneurins instruct synaptic partner matching in an olfactory map.

Hong W, Mosca TJ, Luo L - Nature (2012)

Bottom Line: Ten-m and Ten-a are highly expressed in select PN-ORN matching pairs.Teneurin loss- and gain-of-function cause specific mismatching of select ORNs and PNs.We propose that Teneurins instruct matching specificity between synaptic partners through homophilic attraction.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.

ABSTRACT
Neurons are interconnected with extraordinary precision to assemble a functional nervous system. Compared to axon guidance, far less is understood about how individual pre- and postsynaptic partners are matched. To ensure the proper relay of olfactory information in the fruitfly Drosophila, axons of ∼50 classes of olfactory receptor neurons (ORNs) form one-to-one connections with dendrites of ∼50 classes of projection neurons (PNs). Here, using genetic screens, we identified two evolutionarily conserved, epidermal growth factor (EGF)-repeat containing transmembrane Teneurin proteins, Ten-m and Ten-a, as synaptic-partner-matching molecules between PN dendrites and ORN axons. Ten-m and Ten-a are highly expressed in select PN-ORN matching pairs. Teneurin loss- and gain-of-function cause specific mismatching of select ORNs and PNs. Finally, Teneurins promote homophilic interactions in vitro, and Ten-m co-expression in non-partner PNs and ORNs promotes their ectopic connections in vivo. We propose that Teneurins instruct matching specificity between synaptic partners through homophilic attraction.

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Loss of Teneurins causes PN-ORN mismatchinga, Normally, Mz19 dendrites (green) innervate glomeruli adjacent to the VA1lm glomerulus, which is itself innervated by Or47b axons (red). The dashed line encircles Or47b axons. DC3 PNs are located posterior to DA1/VA1d PNs and Or47b ORNs, and are not visible in these sections. c, Mismatching phenotypes in ten-m and ten-a RNAi driven by the pan-neuronal driver C155-GAL4. Dashed lines encircle Or47b ORN axons, showing intermingling with Mz19 PN dendrites (arrowhead). e, Quantification of Mz19-Or47b mismatching phenotypes. For all genotypes, n≥15. f, In control, DA1 PNs do not intermingle with Or47b ORNs. h, MARCM expression of ten-a RNAi in DA1 PNs causes dendrite intermingling with Or47b axons (arrowhead). j, Quantification of mismatching phenotypes. For all genotypes, n≥6. Error bars represent S.E.M. ***, p<0.001 compared to control. b, d, g, i, Summary showing normal connectivity in control (a, f) and mismatching phenotypes following teneurin RNAi (c, h). Blue: Ten-m high; orange: Ten-a high. Green outlines: labeled PNs. Red outlines: labeled ORNs.
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Figure 3: Loss of Teneurins causes PN-ORN mismatchinga, Normally, Mz19 dendrites (green) innervate glomeruli adjacent to the VA1lm glomerulus, which is itself innervated by Or47b axons (red). The dashed line encircles Or47b axons. DC3 PNs are located posterior to DA1/VA1d PNs and Or47b ORNs, and are not visible in these sections. c, Mismatching phenotypes in ten-m and ten-a RNAi driven by the pan-neuronal driver C155-GAL4. Dashed lines encircle Or47b ORN axons, showing intermingling with Mz19 PN dendrites (arrowhead). e, Quantification of Mz19-Or47b mismatching phenotypes. For all genotypes, n≥15. f, In control, DA1 PNs do not intermingle with Or47b ORNs. h, MARCM expression of ten-a RNAi in DA1 PNs causes dendrite intermingling with Or47b axons (arrowhead). j, Quantification of mismatching phenotypes. For all genotypes, n≥6. Error bars represent S.E.M. ***, p<0.001 compared to control. b, d, g, i, Summary showing normal connectivity in control (a, f) and mismatching phenotypes following teneurin RNAi (c, h). Blue: Ten-m high; orange: Ten-a high. Green outlines: labeled PNs. Red outlines: labeled ORNs.

Mentions: To examine whether Teneurins are required for proper PN-ORN matching, we performed tissue-specific RNAi (Fig. 3, S2c) in all neurons using C155-GAL4, in PNs using GH146-GAL4, or in ORNs using peb-GAL4. To label specific subsets of PN dendrites independent of GAL4-UAS, we used the Q binary expression system30, and converted Mz19-GAL4 to Mz19-QF by BAC recombineering (Fig. S2d). We could thus perform GAL4-based RNAi knockdown while labeling PN dendrites and ORN axons in two colors independent of GAL4. We focused our analysis on Mz19 dendrites and Or47b axons, which innervate neighboring glomeruli but never intermingle in wild type (Fig. 1b, 3a-b).


Teneurins instruct synaptic partner matching in an olfactory map.

Hong W, Mosca TJ, Luo L - Nature (2012)

Loss of Teneurins causes PN-ORN mismatchinga, Normally, Mz19 dendrites (green) innervate glomeruli adjacent to the VA1lm glomerulus, which is itself innervated by Or47b axons (red). The dashed line encircles Or47b axons. DC3 PNs are located posterior to DA1/VA1d PNs and Or47b ORNs, and are not visible in these sections. c, Mismatching phenotypes in ten-m and ten-a RNAi driven by the pan-neuronal driver C155-GAL4. Dashed lines encircle Or47b ORN axons, showing intermingling with Mz19 PN dendrites (arrowhead). e, Quantification of Mz19-Or47b mismatching phenotypes. For all genotypes, n≥15. f, In control, DA1 PNs do not intermingle with Or47b ORNs. h, MARCM expression of ten-a RNAi in DA1 PNs causes dendrite intermingling with Or47b axons (arrowhead). j, Quantification of mismatching phenotypes. For all genotypes, n≥6. Error bars represent S.E.M. ***, p<0.001 compared to control. b, d, g, i, Summary showing normal connectivity in control (a, f) and mismatching phenotypes following teneurin RNAi (c, h). Blue: Ten-m high; orange: Ten-a high. Green outlines: labeled PNs. Red outlines: labeled ORNs.
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Related In: Results  -  Collection

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Figure 3: Loss of Teneurins causes PN-ORN mismatchinga, Normally, Mz19 dendrites (green) innervate glomeruli adjacent to the VA1lm glomerulus, which is itself innervated by Or47b axons (red). The dashed line encircles Or47b axons. DC3 PNs are located posterior to DA1/VA1d PNs and Or47b ORNs, and are not visible in these sections. c, Mismatching phenotypes in ten-m and ten-a RNAi driven by the pan-neuronal driver C155-GAL4. Dashed lines encircle Or47b ORN axons, showing intermingling with Mz19 PN dendrites (arrowhead). e, Quantification of Mz19-Or47b mismatching phenotypes. For all genotypes, n≥15. f, In control, DA1 PNs do not intermingle with Or47b ORNs. h, MARCM expression of ten-a RNAi in DA1 PNs causes dendrite intermingling with Or47b axons (arrowhead). j, Quantification of mismatching phenotypes. For all genotypes, n≥6. Error bars represent S.E.M. ***, p<0.001 compared to control. b, d, g, i, Summary showing normal connectivity in control (a, f) and mismatching phenotypes following teneurin RNAi (c, h). Blue: Ten-m high; orange: Ten-a high. Green outlines: labeled PNs. Red outlines: labeled ORNs.
Mentions: To examine whether Teneurins are required for proper PN-ORN matching, we performed tissue-specific RNAi (Fig. 3, S2c) in all neurons using C155-GAL4, in PNs using GH146-GAL4, or in ORNs using peb-GAL4. To label specific subsets of PN dendrites independent of GAL4-UAS, we used the Q binary expression system30, and converted Mz19-GAL4 to Mz19-QF by BAC recombineering (Fig. S2d). We could thus perform GAL4-based RNAi knockdown while labeling PN dendrites and ORN axons in two colors independent of GAL4. We focused our analysis on Mz19 dendrites and Or47b axons, which innervate neighboring glomeruli but never intermingle in wild type (Fig. 1b, 3a-b).

Bottom Line: Ten-m and Ten-a are highly expressed in select PN-ORN matching pairs.Teneurin loss- and gain-of-function cause specific mismatching of select ORNs and PNs.We propose that Teneurins instruct matching specificity between synaptic partners through homophilic attraction.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.

ABSTRACT
Neurons are interconnected with extraordinary precision to assemble a functional nervous system. Compared to axon guidance, far less is understood about how individual pre- and postsynaptic partners are matched. To ensure the proper relay of olfactory information in the fruitfly Drosophila, axons of ∼50 classes of olfactory receptor neurons (ORNs) form one-to-one connections with dendrites of ∼50 classes of projection neurons (PNs). Here, using genetic screens, we identified two evolutionarily conserved, epidermal growth factor (EGF)-repeat containing transmembrane Teneurin proteins, Ten-m and Ten-a, as synaptic-partner-matching molecules between PN dendrites and ORN axons. Ten-m and Ten-a are highly expressed in select PN-ORN matching pairs. Teneurin loss- and gain-of-function cause specific mismatching of select ORNs and PNs. Finally, Teneurins promote homophilic interactions in vitro, and Ten-m co-expression in non-partner PNs and ORNs promotes their ectopic connections in vivo. We propose that Teneurins instruct matching specificity between synaptic partners through homophilic attraction.

Show MeSH
Related in: MedlinePlus