Neuropilins define distinct populations of neural crest cells.
Neuropilins define distinct populations of neural crest cells.
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DOI：
10.1186/1749-8104-9-24
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发表时间：
2014-11-03
影响因子：
3.6
通讯作者：
Schwarz Q
中科院分区：
文献类型：
--
作者：
Lumb R;Wiszniak S;Kabbara S;Scherer M;Harvey N;Schwarz Q
神经嵴细胞（NCC）是一种短暂的胚胎细胞类型，可产生多种衍生物，包括感觉和自主神经系统的神经元和神经胶质细胞、头部的黑色素细胞和结缔组织。谱系追踪和功能研究表明，主干 NCC 沿着两条不同的路径迁移，这两条路径与不同的发育命运相关。因此，NCC 通过前体向腹侧迁移形成交感神经节和感觉神经节，而 NCC 向背外侧迁移形成黑素细胞。尽管促进沿背外侧路径迁移的机制已明确，但为沿相同腹侧路径迁移的交感神经和感觉命运 NCC 提供位置识别的分子尚不明确。神经毡蛋白（Nrp1 和 Nrp2）是跨膜糖蛋白，对于 NCC 迁移至关重要。 Nrp1 和 Nrp2 敲除小鼠具有不同的表型，表明这些受体可能在将偏向感觉和交感命运的 NCC 分类到适当位置方面发挥作用。在这里，我们结合了原位杂交、免疫组织化学和谱系追踪分析来证明神经毡蛋白在 NCC 中以非重叠模式表达。 Nrp1 在从后脑菱形核 4 (r4) 移出的 NCC 和产生交感神经节和感觉神经节的躯干 NCC 中表达，而 Nrp2 优先在从 r2 移出的 NCC 和产生感觉神经节的躯干 NCC 中表达。通过生成他莫昔芬诱导的谱系追踪系统，我们进一步证明表达 Nrp2 的 NCC 特异性地填充感觉神经节，包括头部的三叉神经节 (V) 和躯干的背根神经节。综上所述，我们的结果表明 Nrp1 和 Nrp2 在不同的 NCC 群体中表达，并且表达 Nrp2 的 NCC 强烈偏向于感觉命运。在躯干中，表达 Nrp2 的 NCC 特异性产生感觉神经节，而表达 Nrp1 的 NCC 可能产生感觉神经节和交感神经节。因此，我们的研究结果表明，神经毡蛋白在协调 NCC 迁移与命运规范方面发挥着重要作用。
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. 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. 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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