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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >SEROTONIN REGULATES MOUSE CRANIAL NEURAL CREST MIGRATION
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SEROTONIN REGULATES MOUSE CRANIAL NEURAL CREST MIGRATION

机译：血清素调节小鼠颅神经C的迁移

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摘要

Serotonergic agents (uptake inhibitors, receptor ligands) cause significant craniofacial malformations in cultured mouse embryos suggesting that 5-hydroxytryptamine (serotonin) (5-HT) may be an important regulator of craniofacial development. To determine whether serotonergic regulation of cell migration might underly some of these effects, cranial neural crest (NC) explants from embryonic day 9 (E9) (plug day = E1) mouse embryos or dissociated mandibular mesenchyme cells (derived from NC) from E12 embryos were placed in a modified Boyden chamber to measure effects of serotonergic agents on cell migration, A dose-dependent effect of 5-HT on the migration of highly motile cranial NC cells was demonstrated, such that low concentrations of 5-HT stimulated migration, whereas this effect was progressively lost as the dose of 5-HT was increased. In contrast, most concentrations of 5-HT inhibited migration of less motile, mandibular mesenchyme cells. To investigate the possible involvement of specific 5-HT receptors in the stimulation of NC migration, several 5-HT subtype-selective antagonists were used to block the effects of the most stimulatory dose of 5-HT (0.01 mu M) Only NAN-190 (a 5-HT1A antagonist) inhibited the effect of 5-HT, suggesting involvement of this receptor. Further evidence was obtained by using immunohistochemistry with 5-HT receptor antibodies, which revealed expression of the 5-HT1A receptor but not other subtypes by migrating NC cells in both embryos and cranial NC explants. These results suggest that by activating appropriate receptors 5-HT may regulate migration of cranial NC cells and their mesenchymal derivatives in the mouse embryo. [References: 39]
机译：血清素能药物（摄取抑制剂，受体配体）在培养的小鼠胚胎中引起严重的颅面畸形，表明5-羟基色胺（5-羟色胺）（5-HT）可能是颅面发育的重要调节剂。为了确定细胞迁移的血清素调节是否可能是其中某些作用的潜在原因，从胚胎第9天（E9）（插入天= E1）小鼠胚胎或从E12胚胎分离的下颌间充质细胞（来自NC）的颅神经rest（NC）外植体将其置于改良的Boyden室中以测量血清素能药物对细胞迁移的影响。证实了5-HT对高能动颅NC细胞迁移的剂量依赖性作用，因此低浓度的5-HT刺激了迁移，而随着5-HT剂量的增加，这种作用逐渐消失。相比之下，大多数浓度的5-HT会抑制运动较少的下颌间充质细胞的迁移。为了研究特定5-HT受体可能参与刺激NC迁移，使用了几种5-HT亚型选择性拮抗剂来阻断最刺激剂量的5-HT（0.01μM）仅NAN-190 （5-HT1A拮抗剂）抑制了5-HT的作用，表明该受体的参与。通过使用具有5-HT受体抗体的免疫组织化学获得了进一步的证据，该抗体通过使NC细胞在胚胎和颅内NC外植体中迁移，揭示了5-HT1A受体的表达，但没有其他亚型的表达。这些结果表明，通过激活合适的受体5-HT可以调节小鼠胚胎中颅NC细胞及其间充质衍生物的迁移。 [参考：39]

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