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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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PN-ORN synaptic matching screens identify two Teneurinsa, d, Schematics showing two PN-ORN matching screens. PN dendrites are labeled by Mz19-GAL4 driving mCD8GFP and ORN axons by Or47b-rCD2 (a) or Or88a-rCD2 (d). Candidate cell-surface molecules are overexpressed only in Mz19 PNs. b-c, Or47b axons and Mz19 dendrites do not overlap in control (b), but form ectopic connections following Ten-m overexpression (c), as seen by axon-dendrite intermingling (arrowhead). e-f, Or88a axons and Mz19 dendrites connect at the VA1d glomerulus in control (e), but the connection is partially lost following Ten-a overexpression, as part of Or88a axons no longer intermingle with Mz19 dendrites (arrowhead). Target areas of Or47b (b-c) or Or88a (e-f) axons are outlined. Mismatching phenotypes are quantified in Fig. S9k and S10q. The first three columns in b,c,e,f show separate channels of the same section; the fourth shows higher magnification of the dashed squares (as in Fig. 3, 4, 5d-g.). Unless indicated, all images in this and subsequent figures are single confocal sections and all scale bars are 10 μm. g, Domain composition of Drosophila Ten-m and Ten-a. h, Phylogeny of the Drosophila Teneurins and related proteins in other species. Branch lengths represent units of substitutions per site of the sequence alignment. Teneurins are evolutionarily conserved in bilaterians and a unicellular choanoflagellate Monosiga brevicollis, but not in cnidarians.
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Figure 1: PN-ORN synaptic matching screens identify two Teneurinsa, d, Schematics showing two PN-ORN matching screens. PN dendrites are labeled by Mz19-GAL4 driving mCD8GFP and ORN axons by Or47b-rCD2 (a) or Or88a-rCD2 (d). Candidate cell-surface molecules are overexpressed only in Mz19 PNs. b-c, Or47b axons and Mz19 dendrites do not overlap in control (b), but form ectopic connections following Ten-m overexpression (c), as seen by axon-dendrite intermingling (arrowhead). e-f, Or88a axons and Mz19 dendrites connect at the VA1d glomerulus in control (e), but the connection is partially lost following Ten-a overexpression, as part of Or88a axons no longer intermingle with Mz19 dendrites (arrowhead). Target areas of Or47b (b-c) or Or88a (e-f) axons are outlined. Mismatching phenotypes are quantified in Fig. S9k and S10q. The first three columns in b,c,e,f show separate channels of the same section; the fourth shows higher magnification of the dashed squares (as in Fig. 3, 4, 5d-g.). Unless indicated, all images in this and subsequent figures are single confocal sections and all scale bars are 10 μm. g, Domain composition of Drosophila Ten-m and Ten-a. h, Phylogeny of the Drosophila Teneurins and related proteins in other species. Branch lengths represent units of substitutions per site of the sequence alignment. Teneurins are evolutionarily conserved in bilaterians and a unicellular choanoflagellate Monosiga brevicollis, but not in cnidarians.

Mentions: To identify potential PN-ORN matching molecules, we simultaneously labeled select PN dendrites and ORN axons in two colors and performed two complementary genetic screens (Fig. 1a,d). We overexpressed 410 candidate cell-surface molecules, comprising ~40% of the potential cell-recognition molecules in Drosophila16. In the first screen, we used Mz19-GAL4 to label DA1, VA1d and DC3 PNs (hereafter Mz19 PNs), and Or47b-rCD2 to label Or47b ORNs (Fig. 1a,b). Or47b ORN axons normally project to the VA1lm glomerulus and are adjacent to Mz19 PN dendrites without overlap. We overexpressed candidate cell-surface molecules only in Mz19 PNs to identify those that promoted ectopic connections between Or47b axons and Mz19 dendrites (Fig. 1a). We found that overexpression of ten-m (P[GS]9267, Fig. S2b) produced ectopic connections (Fig. 1c).


Teneurins instruct synaptic partner matching in an olfactory map.

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

PN-ORN synaptic matching screens identify two Teneurinsa, d, Schematics showing two PN-ORN matching screens. PN dendrites are labeled by Mz19-GAL4 driving mCD8GFP and ORN axons by Or47b-rCD2 (a) or Or88a-rCD2 (d). Candidate cell-surface molecules are overexpressed only in Mz19 PNs. b-c, Or47b axons and Mz19 dendrites do not overlap in control (b), but form ectopic connections following Ten-m overexpression (c), as seen by axon-dendrite intermingling (arrowhead). e-f, Or88a axons and Mz19 dendrites connect at the VA1d glomerulus in control (e), but the connection is partially lost following Ten-a overexpression, as part of Or88a axons no longer intermingle with Mz19 dendrites (arrowhead). Target areas of Or47b (b-c) or Or88a (e-f) axons are outlined. Mismatching phenotypes are quantified in Fig. S9k and S10q. The first three columns in b,c,e,f show separate channels of the same section; the fourth shows higher magnification of the dashed squares (as in Fig. 3, 4, 5d-g.). Unless indicated, all images in this and subsequent figures are single confocal sections and all scale bars are 10 μm. g, Domain composition of Drosophila Ten-m and Ten-a. h, Phylogeny of the Drosophila Teneurins and related proteins in other species. Branch lengths represent units of substitutions per site of the sequence alignment. Teneurins are evolutionarily conserved in bilaterians and a unicellular choanoflagellate Monosiga brevicollis, but not in cnidarians.
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Related In: Results  -  Collection

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Figure 1: PN-ORN synaptic matching screens identify two Teneurinsa, d, Schematics showing two PN-ORN matching screens. PN dendrites are labeled by Mz19-GAL4 driving mCD8GFP and ORN axons by Or47b-rCD2 (a) or Or88a-rCD2 (d). Candidate cell-surface molecules are overexpressed only in Mz19 PNs. b-c, Or47b axons and Mz19 dendrites do not overlap in control (b), but form ectopic connections following Ten-m overexpression (c), as seen by axon-dendrite intermingling (arrowhead). e-f, Or88a axons and Mz19 dendrites connect at the VA1d glomerulus in control (e), but the connection is partially lost following Ten-a overexpression, as part of Or88a axons no longer intermingle with Mz19 dendrites (arrowhead). Target areas of Or47b (b-c) or Or88a (e-f) axons are outlined. Mismatching phenotypes are quantified in Fig. S9k and S10q. The first three columns in b,c,e,f show separate channels of the same section; the fourth shows higher magnification of the dashed squares (as in Fig. 3, 4, 5d-g.). Unless indicated, all images in this and subsequent figures are single confocal sections and all scale bars are 10 μm. g, Domain composition of Drosophila Ten-m and Ten-a. h, Phylogeny of the Drosophila Teneurins and related proteins in other species. Branch lengths represent units of substitutions per site of the sequence alignment. Teneurins are evolutionarily conserved in bilaterians and a unicellular choanoflagellate Monosiga brevicollis, but not in cnidarians.
Mentions: To identify potential PN-ORN matching molecules, we simultaneously labeled select PN dendrites and ORN axons in two colors and performed two complementary genetic screens (Fig. 1a,d). We overexpressed 410 candidate cell-surface molecules, comprising ~40% of the potential cell-recognition molecules in Drosophila16. In the first screen, we used Mz19-GAL4 to label DA1, VA1d and DC3 PNs (hereafter Mz19 PNs), and Or47b-rCD2 to label Or47b ORNs (Fig. 1a,b). Or47b ORN axons normally project to the VA1lm glomerulus and are adjacent to Mz19 PN dendrites without overlap. We overexpressed candidate cell-surface molecules only in Mz19 PNs to identify those that promoted ectopic connections between Or47b axons and Mz19 dendrites (Fig. 1a). We found that overexpression of ten-m (P[GS]9267, Fig. S2b) produced ectopic connections (Fig. 1c).

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