Limits...
Dendritic targeting in the leg neuropil of Drosophila: the role of midline signalling molecules in generating a myotopic map.

Brierley DJ, Blanc E, Reddy OV, Vijayraghavan K, Williams DW - PLoS Biol. (2009)

Bottom Line: Thus the cellular distinctions in peripheral targets and central dendritic domains, which make up the myotopic map, are linked to the birth-order of these motoneurons.Our developmental analysis of dendrite growth reveals that this myotopic map is generated by targeting.We demonstrate that the medio-lateral positioning of motoneuron dendrites in the leg neuropil is controlled by the midline signalling systems Slit-Robo and Netrin-Fra.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council (MRC) Centre for Developmental Neurobiology, King's College London, London, United Kingdom.

ABSTRACT
Neural maps are emergent, highly ordered structures that are essential for organizing and presenting synaptic information. Within the embryonic nervous system of Drosophila motoneuron dendrites are organized topographically as a myotopic map that reflects their pattern of innervation in the muscle field. Here we reveal that this fundamental organizational principle exists in adult Drosophila, where the dendrites of leg motoneurons also generate a myotopic map. A single postembryonic neuroblast sequentially generates different leg motoneuron subtypes, starting with those innervating proximal targets and medial neuropil regions and producing progeny that innervate distal muscle targets and lateral neuropil later in the lineage. Thus the cellular distinctions in peripheral targets and central dendritic domains, which make up the myotopic map, are linked to the birth-order of these motoneurons. Our developmental analysis of dendrite growth reveals that this myotopic map is generated by targeting. We demonstrate that the medio-lateral positioning of motoneuron dendrites in the leg neuropil is controlled by the midline signalling systems Slit-Robo and Netrin-Fra. These results reveal that dendritic targeting plays a major role in the formation of myotopic maps and suggests that the coordinate spatial control of both pre- and postsynaptic elements by global neuropilar signals may be an important mechanism for establishing the specificity of synaptic connections.

Show MeSH
Birth-order dependent projections of lineage 15 in adult Drosophila.(A) Axonal projections of neuroblast clone of lineage 15 motoneurons revealing the three areas innervated in the prothoracic leg. (B) Motoneuron born following heatshock at 48 h AH innervates the pre-tarsal flexor muscle group located in the proximal femur (red arrow). (C) Motoneuron born following heatshock at 96 h AH innervates muscle groups located in the distal tibia (yellow arrow). (D) Cartoon showing segments of prothoracic leg including coxa (c), trochanter (t), femur (f), tibia (ti), and tarsi (ta) and the position of muscle groups innervated by motoneurons born at 48 (red) and 96 h AH (yellow). (E) The central projections of a neuroblast clone of lineage 15. Cell bodies located in a superficial cellular cortex surrounding a dense fibrous neuropil. The primary neurites of lineage 15 enter the anterior cortex and arborize extensively throughout the neuropil. In the anterior leg neuropil dendrites cover lateral territories extending a few processes towards medial territories (arrowhead); in the posterior neuropil, large dendritic branches extend towards and cross the midline and project into the contralateral leg neuropil. The midline (ML) and the lateral edge (LE) were determined by neuroglian staining. Scale bar = 20 µm. (F) Motoneurons born at 48 h AH elaborate their dendrites in medial (M), intermediate (I), and lateral (L) territories. A major posterior branch projects crosses the midline into the contralateral leg neuropil. (G) The dendrites of motoneurons born at 96 h AH are restricted to the intermediate and lateral territories of the leg neuropil. (H) Cartoon showing the organization of the central projections of two leg motoneurons in the prothoracic neuromere. The dendritic fields of 48 h (red) and 96 h AH (yellow) motoneurons within leg neuropil (light gray) surrounded by a cellular cortex (circles). A refers to anterior. Arrow shows the position of paired bundles of lineage 2. (I) Anti-neuroglian staining reveals bundles of adult specific lineages (arrow) and fibrous neuropil in the prothoracic neuromere. The lines indicate the midline and the lateral edge of the leg neuropil in the right hemineuromere. (J) Plot profile histogram reveals the distribution of the dendritic arborizations of eight 48 h AH single motoneurons (red) and eight 96 h AH cells (yellow) within the leg neuropil. The mean centre of arbor mass for eight neurons is denoted by a coloured circle for each subtype and the standard error of each experimental condition and statistical significance between groups *** p<0.001. Arrowheads represent the 33rd percentile for each subtype. SGV, scaled grey value. Scale bar in G applies to F. Scale bars = 20 µm. (K) Cartoon of thoracicoabdominal complex. Blue box indicates right prothoracic hemineuromere.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2737123&req=5

pbio-1000199-g001: Birth-order dependent projections of lineage 15 in adult Drosophila.(A) Axonal projections of neuroblast clone of lineage 15 motoneurons revealing the three areas innervated in the prothoracic leg. (B) Motoneuron born following heatshock at 48 h AH innervates the pre-tarsal flexor muscle group located in the proximal femur (red arrow). (C) Motoneuron born following heatshock at 96 h AH innervates muscle groups located in the distal tibia (yellow arrow). (D) Cartoon showing segments of prothoracic leg including coxa (c), trochanter (t), femur (f), tibia (ti), and tarsi (ta) and the position of muscle groups innervated by motoneurons born at 48 (red) and 96 h AH (yellow). (E) The central projections of a neuroblast clone of lineage 15. Cell bodies located in a superficial cellular cortex surrounding a dense fibrous neuropil. The primary neurites of lineage 15 enter the anterior cortex and arborize extensively throughout the neuropil. In the anterior leg neuropil dendrites cover lateral territories extending a few processes towards medial territories (arrowhead); in the posterior neuropil, large dendritic branches extend towards and cross the midline and project into the contralateral leg neuropil. The midline (ML) and the lateral edge (LE) were determined by neuroglian staining. Scale bar = 20 µm. (F) Motoneurons born at 48 h AH elaborate their dendrites in medial (M), intermediate (I), and lateral (L) territories. A major posterior branch projects crosses the midline into the contralateral leg neuropil. (G) The dendrites of motoneurons born at 96 h AH are restricted to the intermediate and lateral territories of the leg neuropil. (H) Cartoon showing the organization of the central projections of two leg motoneurons in the prothoracic neuromere. The dendritic fields of 48 h (red) and 96 h AH (yellow) motoneurons within leg neuropil (light gray) surrounded by a cellular cortex (circles). A refers to anterior. Arrow shows the position of paired bundles of lineage 2. (I) Anti-neuroglian staining reveals bundles of adult specific lineages (arrow) and fibrous neuropil in the prothoracic neuromere. The lines indicate the midline and the lateral edge of the leg neuropil in the right hemineuromere. (J) Plot profile histogram reveals the distribution of the dendritic arborizations of eight 48 h AH single motoneurons (red) and eight 96 h AH cells (yellow) within the leg neuropil. The mean centre of arbor mass for eight neurons is denoted by a coloured circle for each subtype and the standard error of each experimental condition and statistical significance between groups *** p<0.001. Arrowheads represent the 33rd percentile for each subtype. SGV, scaled grey value. Scale bar in G applies to F. Scale bars = 20 µm. (K) Cartoon of thoracicoabdominal complex. Blue box indicates right prothoracic hemineuromere.

Mentions: To establish which muscles lineage 15 motoneurons innervate, we imaged GFP labelled axons of neuroblast clones directly through the body wall and in the legs of adult flies between 2 and 4 days after eclosion. For lineage 15 motoneurons the most proximal targets are a series of body wall muscles that control the leg, including the extracoxal leg depressor (unpublished data). Axons from the remainder of lineage 15 then travel through the coxa and trochanter to the femur, where they establish connections proximally with the long tendon muscle 2, ltm2 (the pretarsal flexor), and distally with tibia reductor muscle, tirm (the accessory tibial flexor muscle) (Figure 1A and 1D). For appendicular muscle description, see Soler et al. (2004) [28]. The remaining axons pass the femoral-tibial joint and innervate all muscles in the tibia (Figure 1A and 1D). To gain insight into the central organization of this population, we visualized the projections of lineage 15 clones within the prothoracic neuromere (Figure 1H and 1K) of nervous systems counterstained with anti-neuroglian (Figure 1I). Neuroglian is a transmembrane protein that is enriched on the fasiculated primary neurites of adult-specific neurons. In the adult CNS, anti-neuroglian staining reveals a stereotyped scaffold of neurite bundles and tracts that allows us to define positions relative to the midline (Figure 1H and 1I). Neuroblast clones of lineage 15 insert their primary neurites into the anterior region of the leg neuropil (Figure 1E and 1I) and then arborize extensively within it (Figure 1E and 1H). In the anterior neuropil the bulk of the dendrites cover lateral and intermediate territories sending a few processes to the midline, whereas in the posterior there are also branches that extend to and cross the midline (Figure 1E).


Dendritic targeting in the leg neuropil of Drosophila: the role of midline signalling molecules in generating a myotopic map.

Brierley DJ, Blanc E, Reddy OV, Vijayraghavan K, Williams DW - PLoS Biol. (2009)

Birth-order dependent projections of lineage 15 in adult Drosophila.(A) Axonal projections of neuroblast clone of lineage 15 motoneurons revealing the three areas innervated in the prothoracic leg. (B) Motoneuron born following heatshock at 48 h AH innervates the pre-tarsal flexor muscle group located in the proximal femur (red arrow). (C) Motoneuron born following heatshock at 96 h AH innervates muscle groups located in the distal tibia (yellow arrow). (D) Cartoon showing segments of prothoracic leg including coxa (c), trochanter (t), femur (f), tibia (ti), and tarsi (ta) and the position of muscle groups innervated by motoneurons born at 48 (red) and 96 h AH (yellow). (E) The central projections of a neuroblast clone of lineage 15. Cell bodies located in a superficial cellular cortex surrounding a dense fibrous neuropil. The primary neurites of lineage 15 enter the anterior cortex and arborize extensively throughout the neuropil. In the anterior leg neuropil dendrites cover lateral territories extending a few processes towards medial territories (arrowhead); in the posterior neuropil, large dendritic branches extend towards and cross the midline and project into the contralateral leg neuropil. The midline (ML) and the lateral edge (LE) were determined by neuroglian staining. Scale bar = 20 µm. (F) Motoneurons born at 48 h AH elaborate their dendrites in medial (M), intermediate (I), and lateral (L) territories. A major posterior branch projects crosses the midline into the contralateral leg neuropil. (G) The dendrites of motoneurons born at 96 h AH are restricted to the intermediate and lateral territories of the leg neuropil. (H) Cartoon showing the organization of the central projections of two leg motoneurons in the prothoracic neuromere. The dendritic fields of 48 h (red) and 96 h AH (yellow) motoneurons within leg neuropil (light gray) surrounded by a cellular cortex (circles). A refers to anterior. Arrow shows the position of paired bundles of lineage 2. (I) Anti-neuroglian staining reveals bundles of adult specific lineages (arrow) and fibrous neuropil in the prothoracic neuromere. The lines indicate the midline and the lateral edge of the leg neuropil in the right hemineuromere. (J) Plot profile histogram reveals the distribution of the dendritic arborizations of eight 48 h AH single motoneurons (red) and eight 96 h AH cells (yellow) within the leg neuropil. The mean centre of arbor mass for eight neurons is denoted by a coloured circle for each subtype and the standard error of each experimental condition and statistical significance between groups *** p<0.001. Arrowheads represent the 33rd percentile for each subtype. SGV, scaled grey value. Scale bar in G applies to F. Scale bars = 20 µm. (K) Cartoon of thoracicoabdominal complex. Blue box indicates right prothoracic hemineuromere.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2737123&req=5

pbio-1000199-g001: Birth-order dependent projections of lineage 15 in adult Drosophila.(A) Axonal projections of neuroblast clone of lineage 15 motoneurons revealing the three areas innervated in the prothoracic leg. (B) Motoneuron born following heatshock at 48 h AH innervates the pre-tarsal flexor muscle group located in the proximal femur (red arrow). (C) Motoneuron born following heatshock at 96 h AH innervates muscle groups located in the distal tibia (yellow arrow). (D) Cartoon showing segments of prothoracic leg including coxa (c), trochanter (t), femur (f), tibia (ti), and tarsi (ta) and the position of muscle groups innervated by motoneurons born at 48 (red) and 96 h AH (yellow). (E) The central projections of a neuroblast clone of lineage 15. Cell bodies located in a superficial cellular cortex surrounding a dense fibrous neuropil. The primary neurites of lineage 15 enter the anterior cortex and arborize extensively throughout the neuropil. In the anterior leg neuropil dendrites cover lateral territories extending a few processes towards medial territories (arrowhead); in the posterior neuropil, large dendritic branches extend towards and cross the midline and project into the contralateral leg neuropil. The midline (ML) and the lateral edge (LE) were determined by neuroglian staining. Scale bar = 20 µm. (F) Motoneurons born at 48 h AH elaborate their dendrites in medial (M), intermediate (I), and lateral (L) territories. A major posterior branch projects crosses the midline into the contralateral leg neuropil. (G) The dendrites of motoneurons born at 96 h AH are restricted to the intermediate and lateral territories of the leg neuropil. (H) Cartoon showing the organization of the central projections of two leg motoneurons in the prothoracic neuromere. The dendritic fields of 48 h (red) and 96 h AH (yellow) motoneurons within leg neuropil (light gray) surrounded by a cellular cortex (circles). A refers to anterior. Arrow shows the position of paired bundles of lineage 2. (I) Anti-neuroglian staining reveals bundles of adult specific lineages (arrow) and fibrous neuropil in the prothoracic neuromere. The lines indicate the midline and the lateral edge of the leg neuropil in the right hemineuromere. (J) Plot profile histogram reveals the distribution of the dendritic arborizations of eight 48 h AH single motoneurons (red) and eight 96 h AH cells (yellow) within the leg neuropil. The mean centre of arbor mass for eight neurons is denoted by a coloured circle for each subtype and the standard error of each experimental condition and statistical significance between groups *** p<0.001. Arrowheads represent the 33rd percentile for each subtype. SGV, scaled grey value. Scale bar in G applies to F. Scale bars = 20 µm. (K) Cartoon of thoracicoabdominal complex. Blue box indicates right prothoracic hemineuromere.
Mentions: To establish which muscles lineage 15 motoneurons innervate, we imaged GFP labelled axons of neuroblast clones directly through the body wall and in the legs of adult flies between 2 and 4 days after eclosion. For lineage 15 motoneurons the most proximal targets are a series of body wall muscles that control the leg, including the extracoxal leg depressor (unpublished data). Axons from the remainder of lineage 15 then travel through the coxa and trochanter to the femur, where they establish connections proximally with the long tendon muscle 2, ltm2 (the pretarsal flexor), and distally with tibia reductor muscle, tirm (the accessory tibial flexor muscle) (Figure 1A and 1D). For appendicular muscle description, see Soler et al. (2004) [28]. The remaining axons pass the femoral-tibial joint and innervate all muscles in the tibia (Figure 1A and 1D). To gain insight into the central organization of this population, we visualized the projections of lineage 15 clones within the prothoracic neuromere (Figure 1H and 1K) of nervous systems counterstained with anti-neuroglian (Figure 1I). Neuroglian is a transmembrane protein that is enriched on the fasiculated primary neurites of adult-specific neurons. In the adult CNS, anti-neuroglian staining reveals a stereotyped scaffold of neurite bundles and tracts that allows us to define positions relative to the midline (Figure 1H and 1I). Neuroblast clones of lineage 15 insert their primary neurites into the anterior region of the leg neuropil (Figure 1E and 1I) and then arborize extensively within it (Figure 1E and 1H). In the anterior neuropil the bulk of the dendrites cover lateral and intermediate territories sending a few processes to the midline, whereas in the posterior there are also branches that extend to and cross the midline (Figure 1E).

Bottom Line: Thus the cellular distinctions in peripheral targets and central dendritic domains, which make up the myotopic map, are linked to the birth-order of these motoneurons.Our developmental analysis of dendrite growth reveals that this myotopic map is generated by targeting.We demonstrate that the medio-lateral positioning of motoneuron dendrites in the leg neuropil is controlled by the midline signalling systems Slit-Robo and Netrin-Fra.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council (MRC) Centre for Developmental Neurobiology, King's College London, London, United Kingdom.

ABSTRACT
Neural maps are emergent, highly ordered structures that are essential for organizing and presenting synaptic information. Within the embryonic nervous system of Drosophila motoneuron dendrites are organized topographically as a myotopic map that reflects their pattern of innervation in the muscle field. Here we reveal that this fundamental organizational principle exists in adult Drosophila, where the dendrites of leg motoneurons also generate a myotopic map. A single postembryonic neuroblast sequentially generates different leg motoneuron subtypes, starting with those innervating proximal targets and medial neuropil regions and producing progeny that innervate distal muscle targets and lateral neuropil later in the lineage. Thus the cellular distinctions in peripheral targets and central dendritic domains, which make up the myotopic map, are linked to the birth-order of these motoneurons. Our developmental analysis of dendrite growth reveals that this myotopic map is generated by targeting. We demonstrate that the medio-lateral positioning of motoneuron dendrites in the leg neuropil is controlled by the midline signalling systems Slit-Robo and Netrin-Fra. These results reveal that dendritic targeting plays a major role in the formation of myotopic maps and suggests that the coordinate spatial control of both pre- and postsynaptic elements by global neuropilar signals may be an important mechanism for establishing the specificity of synaptic connections.

Show MeSH