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Positional cues in the Drosophila nerve cord: semaphorins pattern the dorso-ventral axis.

Zlatic M, Li F, Strigini M, Grueber W, Bate M - PLoS Biol. (2009)

Bottom Line: The range of alternative targets is reduced by well organised patterns of growth, termination, and branching that deliver the terminals of appropriate pre- and postsynaptic partners to restricted volumes of the developing nervous system.We show that a combination of Plexin A (Plex A) and Plexin B (Plex B) receptors specifies the ventral projection of sensory neurons by responding to high concentrations of Semaphorin 1a (Sema 1a) and Semaphorin 2a (Sema 2a).Together our findings support the idea that axons are delivered to particular regions of the neuropile by their responses to systems of positional cues in each dimension.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Cambridge, Cambridge, United Kingdom. zlaticm@janelia.hhmi.org

ABSTRACT
During the development of neural circuitry, neurons of different kinds establish specific synaptic connections by selecting appropriate targets from large numbers of alternatives. The range of alternative targets is reduced by well organised patterns of growth, termination, and branching that deliver the terminals of appropriate pre- and postsynaptic partners to restricted volumes of the developing nervous system. We use the axons of embryonic Drosophila sensory neurons as a model system in which to study the way in which growing neurons are guided to terminate in specific volumes of the developing nervous system. The mediolateral positions of sensory arbors are controlled by the response of Robo receptors to a Slit gradient. Here we make a genetic analysis of factors regulating position in the dorso-ventral axis. We find that dorso-ventral layers of neuropile contain different levels and combinations of Semaphorins. We demonstrate the existence of a central to dorsal and central to ventral gradient of Sema 2a, perpendicular to the Slit gradient. We show that a combination of Plexin A (Plex A) and Plexin B (Plex B) receptors specifies the ventral projection of sensory neurons by responding to high concentrations of Semaphorin 1a (Sema 1a) and Semaphorin 2a (Sema 2a). Together our findings support the idea that axons are delivered to particular regions of the neuropile by their responses to systems of positional cues in each dimension.

Show MeSH
Effects of altering levels of receptors for Slit, Sema 2a, or Sema 1a in sensory neurons and the distribution of cues in neuropile.(A–E) Representative images of sensory terminals labelled with PO163GAL4, UAS-n-syb-GFP (green) with respect to Fas II tracts (red) in 21-h embryos (left) and diagrams showing patterns of sensory terminals superimposed on wild-type pattern (right). In all cases images show projections of a confocal z series of transverse sections through A7. Dorsal is up. Arrowheads show midline. White lines, layer boundaries. Numbers indicate layers. M, medial; I, intermediate; L, lateral domains. *, p<0.05; **, p<0.01; ***, p<0.001. Scale bar: 10 µm. (A) Wild-type pattern of sensory terminals revealed in A7 in the CNS of PO163GAL4, UAS-n-syb-GFP embryos. (B) Expressing Robo3 in sensory neurons excludes sensory terminals from the medial domain of neuropile. Sensory terminals shift laterally with respect to Fas II tracts. Quantification of the normalised surface area occupied by sensory terminals (sensory area [SA]) in the medial domain (SAM/T = SA[medial]/SA[medial+intermediate+lateral]) reveals a significant decrease (***, p = 9×10−25; Student's t-test; average SAM/T = 0.04; SD = 0.04; n = 30 hemisegments) with respect to wild-type embryos (average SAM/T = 0.3; SD = 0.07; n = 30 hemisegments). (C) Expressing Plex B in sensory neurons results in exclusion of sensory neuron terminals from neuropile layer 2. Quantification of SA in layer 2 (SA2/h = SA(layer 2)/[hemisegment surface area]) reveals a significant decrease (***, p = 4×10−17; Student's t-test; average SA2/h = 0.003; SD = 0.006; n = 32 hemisegments) with respect to wild-type embryos (average SA2/h = 0.06; SD = 0.02; n = 32 hemisegments). (D) Expressing Plex A in sensory neurons results in their exclusion from layer 1 and from intermediate portions of layer 3. Sensory terminals appear compressed into the most medial portion of layers 4, 2, and 3, so that the overall effect is a ventral/medial projection pattern in the form of an arc on both sides of the midline. Quantification of SA1+3+4/h (SA1+3+4/h = SA[layer 1+3+4]/[hemisegment surface area]) reveals a significant decrease (***, p = 2×10−22; Student's t-test; average SA1+3+4/h = 0.1; SD = 0.04; n = 38 hemisegments) with respect to wild-type embryos (average SA1+3+4/h = 0.3; SD = 0.05; n = 32 hemisegments). (E) Co-expressing Robo3 and Plex B in sensory neurons produces a “combination” of Robo 3 and Plex B expression phenotypes. Sensory terminals are now mostly confined to the lateral-most portion of layers 3 and 4. Quantification of SA in the medial domain reveals a significant decrease (***, p = 1×10−14; Student's t-test; average SAM/T = 0.03; SD = 0.05; n = 14 hemisegments) with respect to wild-type embryos (average SAM/T = 0.3; SD = 0.07; n = 30 hemisegments). Quantification of SA in layer 2 reveals a significant decrease (***, p = 6×10−15; Student's t-test; average SA2/h = 0.004; SD = 0.009; n = 32 hemisegments) with respect to wild-type embryos (average SA2/h = 0.06; SD = 0.02; n = 32 hemisegments). (F–I) Immunofluorescence visualisation of Slit, Sema 2a, and Sema 1a (F, G, and J) and mapping of Sema 2a and Sema 1a (white) with respect to Fas II tracts (red) (H and I) in 13-h-old embryos. Images show projections of confocal z series of transverse sections through A7. Dorsal is up. Arrowheads show midline. White lines, layer boundaries. Magenta lines, neuropile outlines. Numbers indicate layers: M, medial; I, intermediate; L, lateral domains. Scale bar: 5 µm. (F) Superposition of Slit (blue), Sema 2a (red), and Sema 1a (green) patterns. (G) Slit is expressed at highest levels at the midline in all dorso-ventral layers of the neuropile. It forms a medial to lateral concentration gradient. (H and I) Mapping of Sema 2a and Sema 1a expression with respect to Fas II tracts. Note that pattern of forming Fas II tracts in 13-h embryos is variable and slightly different from that in 21-h embryos. However, prominent tracts are still readily recognisable reference points. (H) Sema 2a is expressed at high levels in a medio-lateral stripe perpendicular to the midline extending across the central region of neuropile in layer 2 between I2 and I3. It forms central to dorsal and central to ventral concentration gradients. Expression of the Plex B receptor for Sema 2a (see C) shifts sensory terminals away from high Sema 2a levels. (I) Sema1a expression is strongest in layer 1 and in the intermediate portions of layer 3. Sema 1a is very weakly if at all expressed in layer 4 and in the most medial parts of the neuropile. Expression of the Plex A receptor for Sema 1a (see D) results in the exclusion of sensory terminals from regions with high Sema 1a levels. (J) Superposition of Slit and Sema 2a (both white) patterns. Co-expression of Robo 3 and Plex B (see E) shifts sensory terminals from high Slit and Sema 2a levels. (K) Quantification of the Slit gradient from lateral (L) to medial (M) in a hemisegment (n = 12 hemisegments). Note the medial to lateral gradient. (L) Quantification of the Sema 2a gradient from the ventral (V) to dorsal (D) neuropile (n = 9). Note the central to ventral and the central to dorsal gradients.
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pbio-1000135-g002: Effects of altering levels of receptors for Slit, Sema 2a, or Sema 1a in sensory neurons and the distribution of cues in neuropile.(A–E) Representative images of sensory terminals labelled with PO163GAL4, UAS-n-syb-GFP (green) with respect to Fas II tracts (red) in 21-h embryos (left) and diagrams showing patterns of sensory terminals superimposed on wild-type pattern (right). In all cases images show projections of a confocal z series of transverse sections through A7. Dorsal is up. Arrowheads show midline. White lines, layer boundaries. Numbers indicate layers. M, medial; I, intermediate; L, lateral domains. *, p<0.05; **, p<0.01; ***, p<0.001. Scale bar: 10 µm. (A) Wild-type pattern of sensory terminals revealed in A7 in the CNS of PO163GAL4, UAS-n-syb-GFP embryos. (B) Expressing Robo3 in sensory neurons excludes sensory terminals from the medial domain of neuropile. Sensory terminals shift laterally with respect to Fas II tracts. Quantification of the normalised surface area occupied by sensory terminals (sensory area [SA]) in the medial domain (SAM/T = SA[medial]/SA[medial+intermediate+lateral]) reveals a significant decrease (***, p = 9×10−25; Student's t-test; average SAM/T = 0.04; SD = 0.04; n = 30 hemisegments) with respect to wild-type embryos (average SAM/T = 0.3; SD = 0.07; n = 30 hemisegments). (C) Expressing Plex B in sensory neurons results in exclusion of sensory neuron terminals from neuropile layer 2. Quantification of SA in layer 2 (SA2/h = SA(layer 2)/[hemisegment surface area]) reveals a significant decrease (***, p = 4×10−17; Student's t-test; average SA2/h = 0.003; SD = 0.006; n = 32 hemisegments) with respect to wild-type embryos (average SA2/h = 0.06; SD = 0.02; n = 32 hemisegments). (D) Expressing Plex A in sensory neurons results in their exclusion from layer 1 and from intermediate portions of layer 3. Sensory terminals appear compressed into the most medial portion of layers 4, 2, and 3, so that the overall effect is a ventral/medial projection pattern in the form of an arc on both sides of the midline. Quantification of SA1+3+4/h (SA1+3+4/h = SA[layer 1+3+4]/[hemisegment surface area]) reveals a significant decrease (***, p = 2×10−22; Student's t-test; average SA1+3+4/h = 0.1; SD = 0.04; n = 38 hemisegments) with respect to wild-type embryos (average SA1+3+4/h = 0.3; SD = 0.05; n = 32 hemisegments). (E) Co-expressing Robo3 and Plex B in sensory neurons produces a “combination” of Robo 3 and Plex B expression phenotypes. Sensory terminals are now mostly confined to the lateral-most portion of layers 3 and 4. Quantification of SA in the medial domain reveals a significant decrease (***, p = 1×10−14; Student's t-test; average SAM/T = 0.03; SD = 0.05; n = 14 hemisegments) with respect to wild-type embryos (average SAM/T = 0.3; SD = 0.07; n = 30 hemisegments). Quantification of SA in layer 2 reveals a significant decrease (***, p = 6×10−15; Student's t-test; average SA2/h = 0.004; SD = 0.009; n = 32 hemisegments) with respect to wild-type embryos (average SA2/h = 0.06; SD = 0.02; n = 32 hemisegments). (F–I) Immunofluorescence visualisation of Slit, Sema 2a, and Sema 1a (F, G, and J) and mapping of Sema 2a and Sema 1a (white) with respect to Fas II tracts (red) (H and I) in 13-h-old embryos. Images show projections of confocal z series of transverse sections through A7. Dorsal is up. Arrowheads show midline. White lines, layer boundaries. Magenta lines, neuropile outlines. Numbers indicate layers: M, medial; I, intermediate; L, lateral domains. Scale bar: 5 µm. (F) Superposition of Slit (blue), Sema 2a (red), and Sema 1a (green) patterns. (G) Slit is expressed at highest levels at the midline in all dorso-ventral layers of the neuropile. It forms a medial to lateral concentration gradient. (H and I) Mapping of Sema 2a and Sema 1a expression with respect to Fas II tracts. Note that pattern of forming Fas II tracts in 13-h embryos is variable and slightly different from that in 21-h embryos. However, prominent tracts are still readily recognisable reference points. (H) Sema 2a is expressed at high levels in a medio-lateral stripe perpendicular to the midline extending across the central region of neuropile in layer 2 between I2 and I3. It forms central to dorsal and central to ventral concentration gradients. Expression of the Plex B receptor for Sema 2a (see C) shifts sensory terminals away from high Sema 2a levels. (I) Sema1a expression is strongest in layer 1 and in the intermediate portions of layer 3. Sema 1a is very weakly if at all expressed in layer 4 and in the most medial parts of the neuropile. Expression of the Plex A receptor for Sema 1a (see D) results in the exclusion of sensory terminals from regions with high Sema 1a levels. (J) Superposition of Slit and Sema 2a (both white) patterns. Co-expression of Robo 3 and Plex B (see E) shifts sensory terminals from high Slit and Sema 2a levels. (K) Quantification of the Slit gradient from lateral (L) to medial (M) in a hemisegment (n = 12 hemisegments). Note the medial to lateral gradient. (L) Quantification of the Sema 2a gradient from the ventral (V) to dorsal (D) neuropile (n = 9). Note the central to ventral and the central to dorsal gradients.

Mentions: We used PO163GAL4, UAS-n-synaptobrevin-GFP flies to target gene expression selectively to sensory neurons and simultaneously to visualise their terminals (Figure 2A) [14]. As a test of our method, we confirmed that expressing the Robo 3 receptor for Slit in sensory neurons shifts their terminals away from the medial domain of neuropile (Figure 2B) [6].


Positional cues in the Drosophila nerve cord: semaphorins pattern the dorso-ventral axis.

Zlatic M, Li F, Strigini M, Grueber W, Bate M - PLoS Biol. (2009)

Effects of altering levels of receptors for Slit, Sema 2a, or Sema 1a in sensory neurons and the distribution of cues in neuropile.(A–E) Representative images of sensory terminals labelled with PO163GAL4, UAS-n-syb-GFP (green) with respect to Fas II tracts (red) in 21-h embryos (left) and diagrams showing patterns of sensory terminals superimposed on wild-type pattern (right). In all cases images show projections of a confocal z series of transverse sections through A7. Dorsal is up. Arrowheads show midline. White lines, layer boundaries. Numbers indicate layers. M, medial; I, intermediate; L, lateral domains. *, p<0.05; **, p<0.01; ***, p<0.001. Scale bar: 10 µm. (A) Wild-type pattern of sensory terminals revealed in A7 in the CNS of PO163GAL4, UAS-n-syb-GFP embryos. (B) Expressing Robo3 in sensory neurons excludes sensory terminals from the medial domain of neuropile. Sensory terminals shift laterally with respect to Fas II tracts. Quantification of the normalised surface area occupied by sensory terminals (sensory area [SA]) in the medial domain (SAM/T = SA[medial]/SA[medial+intermediate+lateral]) reveals a significant decrease (***, p = 9×10−25; Student's t-test; average SAM/T = 0.04; SD = 0.04; n = 30 hemisegments) with respect to wild-type embryos (average SAM/T = 0.3; SD = 0.07; n = 30 hemisegments). (C) Expressing Plex B in sensory neurons results in exclusion of sensory neuron terminals from neuropile layer 2. Quantification of SA in layer 2 (SA2/h = SA(layer 2)/[hemisegment surface area]) reveals a significant decrease (***, p = 4×10−17; Student's t-test; average SA2/h = 0.003; SD = 0.006; n = 32 hemisegments) with respect to wild-type embryos (average SA2/h = 0.06; SD = 0.02; n = 32 hemisegments). (D) Expressing Plex A in sensory neurons results in their exclusion from layer 1 and from intermediate portions of layer 3. Sensory terminals appear compressed into the most medial portion of layers 4, 2, and 3, so that the overall effect is a ventral/medial projection pattern in the form of an arc on both sides of the midline. Quantification of SA1+3+4/h (SA1+3+4/h = SA[layer 1+3+4]/[hemisegment surface area]) reveals a significant decrease (***, p = 2×10−22; Student's t-test; average SA1+3+4/h = 0.1; SD = 0.04; n = 38 hemisegments) with respect to wild-type embryos (average SA1+3+4/h = 0.3; SD = 0.05; n = 32 hemisegments). (E) Co-expressing Robo3 and Plex B in sensory neurons produces a “combination” of Robo 3 and Plex B expression phenotypes. Sensory terminals are now mostly confined to the lateral-most portion of layers 3 and 4. Quantification of SA in the medial domain reveals a significant decrease (***, p = 1×10−14; Student's t-test; average SAM/T = 0.03; SD = 0.05; n = 14 hemisegments) with respect to wild-type embryos (average SAM/T = 0.3; SD = 0.07; n = 30 hemisegments). Quantification of SA in layer 2 reveals a significant decrease (***, p = 6×10−15; Student's t-test; average SA2/h = 0.004; SD = 0.009; n = 32 hemisegments) with respect to wild-type embryos (average SA2/h = 0.06; SD = 0.02; n = 32 hemisegments). (F–I) Immunofluorescence visualisation of Slit, Sema 2a, and Sema 1a (F, G, and J) and mapping of Sema 2a and Sema 1a (white) with respect to Fas II tracts (red) (H and I) in 13-h-old embryos. Images show projections of confocal z series of transverse sections through A7. Dorsal is up. Arrowheads show midline. White lines, layer boundaries. Magenta lines, neuropile outlines. Numbers indicate layers: M, medial; I, intermediate; L, lateral domains. Scale bar: 5 µm. (F) Superposition of Slit (blue), Sema 2a (red), and Sema 1a (green) patterns. (G) Slit is expressed at highest levels at the midline in all dorso-ventral layers of the neuropile. It forms a medial to lateral concentration gradient. (H and I) Mapping of Sema 2a and Sema 1a expression with respect to Fas II tracts. Note that pattern of forming Fas II tracts in 13-h embryos is variable and slightly different from that in 21-h embryos. However, prominent tracts are still readily recognisable reference points. (H) Sema 2a is expressed at high levels in a medio-lateral stripe perpendicular to the midline extending across the central region of neuropile in layer 2 between I2 and I3. It forms central to dorsal and central to ventral concentration gradients. Expression of the Plex B receptor for Sema 2a (see C) shifts sensory terminals away from high Sema 2a levels. (I) Sema1a expression is strongest in layer 1 and in the intermediate portions of layer 3. Sema 1a is very weakly if at all expressed in layer 4 and in the most medial parts of the neuropile. Expression of the Plex A receptor for Sema 1a (see D) results in the exclusion of sensory terminals from regions with high Sema 1a levels. (J) Superposition of Slit and Sema 2a (both white) patterns. Co-expression of Robo 3 and Plex B (see E) shifts sensory terminals from high Slit and Sema 2a levels. (K) Quantification of the Slit gradient from lateral (L) to medial (M) in a hemisegment (n = 12 hemisegments). Note the medial to lateral gradient. (L) Quantification of the Sema 2a gradient from the ventral (V) to dorsal (D) neuropile (n = 9). Note the central to ventral and the central to dorsal gradients.
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pbio-1000135-g002: Effects of altering levels of receptors for Slit, Sema 2a, or Sema 1a in sensory neurons and the distribution of cues in neuropile.(A–E) Representative images of sensory terminals labelled with PO163GAL4, UAS-n-syb-GFP (green) with respect to Fas II tracts (red) in 21-h embryos (left) and diagrams showing patterns of sensory terminals superimposed on wild-type pattern (right). In all cases images show projections of a confocal z series of transverse sections through A7. Dorsal is up. Arrowheads show midline. White lines, layer boundaries. Numbers indicate layers. M, medial; I, intermediate; L, lateral domains. *, p<0.05; **, p<0.01; ***, p<0.001. Scale bar: 10 µm. (A) Wild-type pattern of sensory terminals revealed in A7 in the CNS of PO163GAL4, UAS-n-syb-GFP embryos. (B) Expressing Robo3 in sensory neurons excludes sensory terminals from the medial domain of neuropile. Sensory terminals shift laterally with respect to Fas II tracts. Quantification of the normalised surface area occupied by sensory terminals (sensory area [SA]) in the medial domain (SAM/T = SA[medial]/SA[medial+intermediate+lateral]) reveals a significant decrease (***, p = 9×10−25; Student's t-test; average SAM/T = 0.04; SD = 0.04; n = 30 hemisegments) with respect to wild-type embryos (average SAM/T = 0.3; SD = 0.07; n = 30 hemisegments). (C) Expressing Plex B in sensory neurons results in exclusion of sensory neuron terminals from neuropile layer 2. Quantification of SA in layer 2 (SA2/h = SA(layer 2)/[hemisegment surface area]) reveals a significant decrease (***, p = 4×10−17; Student's t-test; average SA2/h = 0.003; SD = 0.006; n = 32 hemisegments) with respect to wild-type embryos (average SA2/h = 0.06; SD = 0.02; n = 32 hemisegments). (D) Expressing Plex A in sensory neurons results in their exclusion from layer 1 and from intermediate portions of layer 3. Sensory terminals appear compressed into the most medial portion of layers 4, 2, and 3, so that the overall effect is a ventral/medial projection pattern in the form of an arc on both sides of the midline. Quantification of SA1+3+4/h (SA1+3+4/h = SA[layer 1+3+4]/[hemisegment surface area]) reveals a significant decrease (***, p = 2×10−22; Student's t-test; average SA1+3+4/h = 0.1; SD = 0.04; n = 38 hemisegments) with respect to wild-type embryos (average SA1+3+4/h = 0.3; SD = 0.05; n = 32 hemisegments). (E) Co-expressing Robo3 and Plex B in sensory neurons produces a “combination” of Robo 3 and Plex B expression phenotypes. Sensory terminals are now mostly confined to the lateral-most portion of layers 3 and 4. Quantification of SA in the medial domain reveals a significant decrease (***, p = 1×10−14; Student's t-test; average SAM/T = 0.03; SD = 0.05; n = 14 hemisegments) with respect to wild-type embryos (average SAM/T = 0.3; SD = 0.07; n = 30 hemisegments). Quantification of SA in layer 2 reveals a significant decrease (***, p = 6×10−15; Student's t-test; average SA2/h = 0.004; SD = 0.009; n = 32 hemisegments) with respect to wild-type embryos (average SA2/h = 0.06; SD = 0.02; n = 32 hemisegments). (F–I) Immunofluorescence visualisation of Slit, Sema 2a, and Sema 1a (F, G, and J) and mapping of Sema 2a and Sema 1a (white) with respect to Fas II tracts (red) (H and I) in 13-h-old embryos. Images show projections of confocal z series of transverse sections through A7. Dorsal is up. Arrowheads show midline. White lines, layer boundaries. Magenta lines, neuropile outlines. Numbers indicate layers: M, medial; I, intermediate; L, lateral domains. Scale bar: 5 µm. (F) Superposition of Slit (blue), Sema 2a (red), and Sema 1a (green) patterns. (G) Slit is expressed at highest levels at the midline in all dorso-ventral layers of the neuropile. It forms a medial to lateral concentration gradient. (H and I) Mapping of Sema 2a and Sema 1a expression with respect to Fas II tracts. Note that pattern of forming Fas II tracts in 13-h embryos is variable and slightly different from that in 21-h embryos. However, prominent tracts are still readily recognisable reference points. (H) Sema 2a is expressed at high levels in a medio-lateral stripe perpendicular to the midline extending across the central region of neuropile in layer 2 between I2 and I3. It forms central to dorsal and central to ventral concentration gradients. Expression of the Plex B receptor for Sema 2a (see C) shifts sensory terminals away from high Sema 2a levels. (I) Sema1a expression is strongest in layer 1 and in the intermediate portions of layer 3. Sema 1a is very weakly if at all expressed in layer 4 and in the most medial parts of the neuropile. Expression of the Plex A receptor for Sema 1a (see D) results in the exclusion of sensory terminals from regions with high Sema 1a levels. (J) Superposition of Slit and Sema 2a (both white) patterns. Co-expression of Robo 3 and Plex B (see E) shifts sensory terminals from high Slit and Sema 2a levels. (K) Quantification of the Slit gradient from lateral (L) to medial (M) in a hemisegment (n = 12 hemisegments). Note the medial to lateral gradient. (L) Quantification of the Sema 2a gradient from the ventral (V) to dorsal (D) neuropile (n = 9). Note the central to ventral and the central to dorsal gradients.
Mentions: We used PO163GAL4, UAS-n-synaptobrevin-GFP flies to target gene expression selectively to sensory neurons and simultaneously to visualise their terminals (Figure 2A) [14]. As a test of our method, we confirmed that expressing the Robo 3 receptor for Slit in sensory neurons shifts their terminals away from the medial domain of neuropile (Figure 2B) [6].

Bottom Line: The range of alternative targets is reduced by well organised patterns of growth, termination, and branching that deliver the terminals of appropriate pre- and postsynaptic partners to restricted volumes of the developing nervous system.We show that a combination of Plexin A (Plex A) and Plexin B (Plex B) receptors specifies the ventral projection of sensory neurons by responding to high concentrations of Semaphorin 1a (Sema 1a) and Semaphorin 2a (Sema 2a).Together our findings support the idea that axons are delivered to particular regions of the neuropile by their responses to systems of positional cues in each dimension.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Cambridge, Cambridge, United Kingdom. zlaticm@janelia.hhmi.org

ABSTRACT
During the development of neural circuitry, neurons of different kinds establish specific synaptic connections by selecting appropriate targets from large numbers of alternatives. The range of alternative targets is reduced by well organised patterns of growth, termination, and branching that deliver the terminals of appropriate pre- and postsynaptic partners to restricted volumes of the developing nervous system. We use the axons of embryonic Drosophila sensory neurons as a model system in which to study the way in which growing neurons are guided to terminate in specific volumes of the developing nervous system. The mediolateral positions of sensory arbors are controlled by the response of Robo receptors to a Slit gradient. Here we make a genetic analysis of factors regulating position in the dorso-ventral axis. We find that dorso-ventral layers of neuropile contain different levels and combinations of Semaphorins. We demonstrate the existence of a central to dorsal and central to ventral gradient of Sema 2a, perpendicular to the Slit gradient. We show that a combination of Plexin A (Plex A) and Plexin B (Plex B) receptors specifies the ventral projection of sensory neurons by responding to high concentrations of Semaphorin 1a (Sema 1a) and Semaphorin 2a (Sema 2a). Together our findings support the idea that axons are delivered to particular regions of the neuropile by their responses to systems of positional cues in each dimension.

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