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Neuropilins define distinct populations of neural crest cells.

Lumb R, Wiszniak S, Kabbara S, Scherer M, Harvey N, Schwarz Q - Neural Dev (2014)

Bottom Line: Taken together, our results demonstrate that Nrp1 and Nrp2 are expressed in different populations of NCCs, and that Nrp2-expressing NCCs are strongly biased towards a sensory fate.In the trunk, Nrp2-expressing NCCs specifically give rise to sensory ganglia, whereas Nrp1-expressing NCCs likely give rise to both sensory and sympathetic ganglia.Our findings therefore suggest that neuropilins play an essential role in coordinating NCC migration with fate specification.

View Article: PubMed Central - PubMed

Affiliation: Centre for Cancer Biology, University of South Australia and SA Pathology, Frome Road, Adelaide 5000, Australia. quenten.schwarz@health.sa.gov.au.

ABSTRACT

Background: Neural crest cells (NCCs) are a transient embryonic cell type that give rise to a wide spectrum of derivatives, including neurons and glia of the sensory and autonomic nervous system, melanocytes and connective tissues in the head. Lineage-tracing and functional studies have shown that trunk NCCs migrate along two distinct paths that correlate with different developmental fates. Thus, NCCs migrating ventrally through the anterior somite form sympathetic and sensory ganglia, whereas NCCs migrating dorsolaterally form melanocytes. Although the mechanisms promoting migration along the dorsolateral path are well defined, the molecules providing positional identity to sympathetic and sensory-fated NCCs that migrate along the same ventral path are ill defined. Neuropilins (Nrp1 and Nrp2) are transmembrane glycoproteins that are essential for NCC migration. Nrp1 and Nrp2 knockout mice have disparate phenotypes, suggesting that these receptors may play a role in sorting NCCs biased towards sensory and sympathetic fates to appropriate locations.

Results: Here we have combined in situ hybridisation, immunohistochemistry and lineage-tracing analyses to demonstrate that neuropilins are expressed in a non-overlapping pattern within NCCs. Whereas Nrp1 is expressed in NCCs emigrating from hindbrain rhombomere 4 (r4) and within trunk NCCs giving rise to sympathetic and sensory ganglia, Nrp2 is preferentially expressed in NCCs emigrating from r2 and in trunk NCCs giving rise to sensory ganglia. By generating a tamoxifen-inducible lineage-tracing system, we further demonstrate that Nrp2-expressing NCCs specifically populate sensory ganglia including the trigeminal ganglia (V) in the head and the dorsal root ganglia in the trunk.

Conclusions: Taken together, our results demonstrate that Nrp1 and Nrp2 are expressed in different populations of NCCs, and that Nrp2-expressing NCCs are strongly biased towards a sensory fate. In the trunk, Nrp2-expressing NCCs specifically give rise to sensory ganglia, whereas Nrp1-expressing NCCs likely give rise to both sensory and sympathetic ganglia. Our findings therefore suggest that neuropilins play an essential role in coordinating NCC migration with fate specification.

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Neuropilins define molecularly distinct populations of ventrally migrating trunk NCCs. (A) Schematic detailing the neuropilin expression profiles in migrating trunk NCCs. NCCs migrating to the dorsal aorta (da) give rise to the sympathetic ganglia, while NCCs that stall within the somite alongside the neural tube (nt) give rise to sensory neurons of the DRG. Trunk NCCs at the level of the forelimb begin to delaminate from the neural tube at E8.5, and by E9.0, have started to migrate within the somite. At E9.5, some NCCs have already reached the dorsal aorta, while others have stalled in the anlagen of the DRG. At E10.5, NCCs with sympathetic fate have condensed, while NCCs with sensory fate have started differentiating in the DRG. Expression profiling identified distinct populations of NCCs with Nrp1 (red), Nrp2 (blue), and Nrp1/Nrp2 (purple). Nrp1-expressing cells preferentially migrate towards the dorsal aorta while Nrp2-expressing cells stall within the area of the DRG. Nrp2 was also expressed in presumptive NCC precursors within the dorsal neural tube. (B) Schematic diagram detailing the fate restriction of trunk NCCs. NCCs delaminate from the neural tube to migrate along two separate paths. Ventrally migrating NCCs initially travel through the intersomitic space to seed the sympathetic ganglia, and then switch to travel ventrally through the anterior half of the somite to give rise to sensory ganglia, sympathetic ganglia, and melanocytes. NCCs migrating dorsolaterally also give rise to melanocytes. Expression, fate-mapping, and phenotypic studies suggest that Nrp2 (Nrp2 alone (blue) and Nrp1/Nrp2 (purple)) is a marker of NCCs biased towards sensory ganglia. In addition, expression and phenotypic studies suggest that Nrp1 (red) is a marker of ventrally migrating NCCs that give rise to sympathetic ganglia.
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Fig9: Neuropilins define molecularly distinct populations of ventrally migrating trunk NCCs. (A) Schematic detailing the neuropilin expression profiles in migrating trunk NCCs. NCCs migrating to the dorsal aorta (da) give rise to the sympathetic ganglia, while NCCs that stall within the somite alongside the neural tube (nt) give rise to sensory neurons of the DRG. Trunk NCCs at the level of the forelimb begin to delaminate from the neural tube at E8.5, and by E9.0, have started to migrate within the somite. At E9.5, some NCCs have already reached the dorsal aorta, while others have stalled in the anlagen of the DRG. At E10.5, NCCs with sympathetic fate have condensed, while NCCs with sensory fate have started differentiating in the DRG. Expression profiling identified distinct populations of NCCs with Nrp1 (red), Nrp2 (blue), and Nrp1/Nrp2 (purple). Nrp1-expressing cells preferentially migrate towards the dorsal aorta while Nrp2-expressing cells stall within the area of the DRG. Nrp2 was also expressed in presumptive NCC precursors within the dorsal neural tube. (B) Schematic diagram detailing the fate restriction of trunk NCCs. NCCs delaminate from the neural tube to migrate along two separate paths. Ventrally migrating NCCs initially travel through the intersomitic space to seed the sympathetic ganglia, and then switch to travel ventrally through the anterior half of the somite to give rise to sensory ganglia, sympathetic ganglia, and melanocytes. NCCs migrating dorsolaterally also give rise to melanocytes. Expression, fate-mapping, and phenotypic studies suggest that Nrp2 (Nrp2 alone (blue) and Nrp1/Nrp2 (purple)) is a marker of NCCs biased towards sensory ganglia. In addition, expression and phenotypic studies suggest that Nrp1 (red) is a marker of ventrally migrating NCCs that give rise to sympathetic ganglia.

Mentions: The work presented here identified molecularly distinct populations of cranial and trunk NCCs based on their expression profiles of the cell surface receptors Nrp1 and Nrp2. In combination with the recent analyses of Nrp1 and Nrp2 knockout mice [31–34], this work further identifies essential roles for neuropilins in sorting specific populations of NCCs to their final destinations within the embryo (Figure 9A). In the head, Nrp1 is expressed in NCCs emigrating from r4, and is required for the migration and condensation of neurons and glia of the facio-acoustic ganglion (VII-VIII) [31]. By contrast, Nrp2 is expressed in NCCs emigrating from r2, and is required for the migration and condensation of neurons and glia of the trigeminal ganglion (V) [32].Figure 9


Neuropilins define distinct populations of neural crest cells.

Lumb R, Wiszniak S, Kabbara S, Scherer M, Harvey N, Schwarz Q - Neural Dev (2014)

Neuropilins define molecularly distinct populations of ventrally migrating trunk NCCs. (A) Schematic detailing the neuropilin expression profiles in migrating trunk NCCs. NCCs migrating to the dorsal aorta (da) give rise to the sympathetic ganglia, while NCCs that stall within the somite alongside the neural tube (nt) give rise to sensory neurons of the DRG. Trunk NCCs at the level of the forelimb begin to delaminate from the neural tube at E8.5, and by E9.0, have started to migrate within the somite. At E9.5, some NCCs have already reached the dorsal aorta, while others have stalled in the anlagen of the DRG. At E10.5, NCCs with sympathetic fate have condensed, while NCCs with sensory fate have started differentiating in the DRG. Expression profiling identified distinct populations of NCCs with Nrp1 (red), Nrp2 (blue), and Nrp1/Nrp2 (purple). Nrp1-expressing cells preferentially migrate towards the dorsal aorta while Nrp2-expressing cells stall within the area of the DRG. Nrp2 was also expressed in presumptive NCC precursors within the dorsal neural tube. (B) Schematic diagram detailing the fate restriction of trunk NCCs. NCCs delaminate from the neural tube to migrate along two separate paths. Ventrally migrating NCCs initially travel through the intersomitic space to seed the sympathetic ganglia, and then switch to travel ventrally through the anterior half of the somite to give rise to sensory ganglia, sympathetic ganglia, and melanocytes. NCCs migrating dorsolaterally also give rise to melanocytes. Expression, fate-mapping, and phenotypic studies suggest that Nrp2 (Nrp2 alone (blue) and Nrp1/Nrp2 (purple)) is a marker of NCCs biased towards sensory ganglia. In addition, expression and phenotypic studies suggest that Nrp1 (red) is a marker of ventrally migrating NCCs that give rise to sympathetic ganglia.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Fig9: Neuropilins define molecularly distinct populations of ventrally migrating trunk NCCs. (A) Schematic detailing the neuropilin expression profiles in migrating trunk NCCs. NCCs migrating to the dorsal aorta (da) give rise to the sympathetic ganglia, while NCCs that stall within the somite alongside the neural tube (nt) give rise to sensory neurons of the DRG. Trunk NCCs at the level of the forelimb begin to delaminate from the neural tube at E8.5, and by E9.0, have started to migrate within the somite. At E9.5, some NCCs have already reached the dorsal aorta, while others have stalled in the anlagen of the DRG. At E10.5, NCCs with sympathetic fate have condensed, while NCCs with sensory fate have started differentiating in the DRG. Expression profiling identified distinct populations of NCCs with Nrp1 (red), Nrp2 (blue), and Nrp1/Nrp2 (purple). Nrp1-expressing cells preferentially migrate towards the dorsal aorta while Nrp2-expressing cells stall within the area of the DRG. Nrp2 was also expressed in presumptive NCC precursors within the dorsal neural tube. (B) Schematic diagram detailing the fate restriction of trunk NCCs. NCCs delaminate from the neural tube to migrate along two separate paths. Ventrally migrating NCCs initially travel through the intersomitic space to seed the sympathetic ganglia, and then switch to travel ventrally through the anterior half of the somite to give rise to sensory ganglia, sympathetic ganglia, and melanocytes. NCCs migrating dorsolaterally also give rise to melanocytes. Expression, fate-mapping, and phenotypic studies suggest that Nrp2 (Nrp2 alone (blue) and Nrp1/Nrp2 (purple)) is a marker of NCCs biased towards sensory ganglia. In addition, expression and phenotypic studies suggest that Nrp1 (red) is a marker of ventrally migrating NCCs that give rise to sympathetic ganglia.
Mentions: The work presented here identified molecularly distinct populations of cranial and trunk NCCs based on their expression profiles of the cell surface receptors Nrp1 and Nrp2. In combination with the recent analyses of Nrp1 and Nrp2 knockout mice [31–34], this work further identifies essential roles for neuropilins in sorting specific populations of NCCs to their final destinations within the embryo (Figure 9A). In the head, Nrp1 is expressed in NCCs emigrating from r4, and is required for the migration and condensation of neurons and glia of the facio-acoustic ganglion (VII-VIII) [31]. By contrast, Nrp2 is expressed in NCCs emigrating from r2, and is required for the migration and condensation of neurons and glia of the trigeminal ganglion (V) [32].Figure 9

Bottom Line: Taken together, our results demonstrate that Nrp1 and Nrp2 are expressed in different populations of NCCs, and that Nrp2-expressing NCCs are strongly biased towards a sensory fate.In the trunk, Nrp2-expressing NCCs specifically give rise to sensory ganglia, whereas Nrp1-expressing NCCs likely give rise to both sensory and sympathetic ganglia.Our findings therefore suggest that neuropilins play an essential role in coordinating NCC migration with fate specification.

View Article: PubMed Central - PubMed

Affiliation: Centre for Cancer Biology, University of South Australia and SA Pathology, Frome Road, Adelaide 5000, Australia. quenten.schwarz@health.sa.gov.au.

ABSTRACT

Background: Neural crest cells (NCCs) are a transient embryonic cell type that give rise to a wide spectrum of derivatives, including neurons and glia of the sensory and autonomic nervous system, melanocytes and connective tissues in the head. Lineage-tracing and functional studies have shown that trunk NCCs migrate along two distinct paths that correlate with different developmental fates. Thus, NCCs migrating ventrally through the anterior somite form sympathetic and sensory ganglia, whereas NCCs migrating dorsolaterally form melanocytes. Although the mechanisms promoting migration along the dorsolateral path are well defined, the molecules providing positional identity to sympathetic and sensory-fated NCCs that migrate along the same ventral path are ill defined. Neuropilins (Nrp1 and Nrp2) are transmembrane glycoproteins that are essential for NCC migration. Nrp1 and Nrp2 knockout mice have disparate phenotypes, suggesting that these receptors may play a role in sorting NCCs biased towards sensory and sympathetic fates to appropriate locations.

Results: Here we have combined in situ hybridisation, immunohistochemistry and lineage-tracing analyses to demonstrate that neuropilins are expressed in a non-overlapping pattern within NCCs. Whereas Nrp1 is expressed in NCCs emigrating from hindbrain rhombomere 4 (r4) and within trunk NCCs giving rise to sympathetic and sensory ganglia, Nrp2 is preferentially expressed in NCCs emigrating from r2 and in trunk NCCs giving rise to sensory ganglia. By generating a tamoxifen-inducible lineage-tracing system, we further demonstrate that Nrp2-expressing NCCs specifically populate sensory ganglia including the trigeminal ganglia (V) in the head and the dorsal root ganglia in the trunk.

Conclusions: Taken together, our results demonstrate that Nrp1 and Nrp2 are expressed in different populations of NCCs, and that Nrp2-expressing NCCs are strongly biased towards a sensory fate. In the trunk, Nrp2-expressing NCCs specifically give rise to sensory ganglia, whereas Nrp1-expressing NCCs likely give rise to both sensory and sympathetic ganglia. Our findings therefore suggest that neuropilins play an essential role in coordinating NCC migration with fate specification.

Show MeSH
Related in: MedlinePlus