Abstract
BackgroundNeural 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.ResultsHere 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.ConclusionsTaken 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.
Highlights
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
By comparing the expression profiles of Neuropilin 1 (Nrp1) and Neuropilin 2 (Nrp2) with that of the pan-NCC marker Sox10, we found that neuropilins are expressed in different populations of cranial NCCs
At E8.5 and E9.0, the time at which NCCs have delaminated from the neural tube and begun to migrate into the branchial arch tissue, the expression of Nrp1 was restricted to the stream of NCCs emigrating out of r4, while Nrp2 was expressed reciprocally within NCCs emigrating out of r2 (Figure 1A-F)
Summary
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. Vagal NCCs arise from the level of somites 1 to 7, and produce enteric NCCs that form the neurons and glia of the enteric nervous system [3], and other cell types such as cardiac NCCs (level of somites 1 to 3) that form vascular smooth muscle lining the great arteries and contribute to the aortic– pulmonary septum [4] Even within these anatomically defined domains, NCCs can be further subdivided by additional properties, including their migration path and their developmental fate [5,6,7]. A fundamental question for this field is how NCCs navigate their environment to position themselves in appropriate locations
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