PDF(Pubmed)
Abstract：
Many processes take place during embryogenesis, and the development of the palate mainly involves proliferation, migration, osteogenesis, and epithelial-mesenchymal transition. Abnormalities in any of these processes can be the cause of cleft palate (CP). There have been few reports on whether C-X-C motif chemokine receptor 4 (CXCR4), which is involved in embryonic development, participates in these processes. In our study, the knockdown of Cxcr4 inhibited the migration of mouse embryonic palatal mesenchymal (MEPM) cells similarly to the use of its inhibitor plerixafor, and the inhibition of cell migration in the Cxcr4 knockdown group was partially reversed by supplementation with C-X-C motif chemokine ligand 12 (CXCL12). In combination with low-dose retinoic acid (RA), plerixafor increased the incidence of cleft palates in mice by decreasing the expression of Cxcr4 and its downstream migration-regulating gene Rac family small GTPase 1 (RAC1) mediating actin cytoskeleton to affect lamellipodia formation and focal complex assembly and ras homolog family member A (RHOA) regulating the actin cytoskeleton to affect stress fiber formation and focal complex maturation into focal adhesions. Our results indicate that the disruption of cell migration and impaired normal palatal development by inhibition of Cxcr4 expression might be mediated through Rac1 with RhoA. The combination of retinoic acid and plerixafor might increase the incidence of cleft palate, which also provided a rationale to guide the use of the drug during conception.
摘要：
许多过程发生在胚胎发生过程中，腭的发育主要涉及增殖，迁移,成骨,和上皮-间质转化。这些过程中的任何一个异常都可能是c裂（CP）的原因。关于C-X-C基序趋化因子受体4(CXCR4),参与胚胎发育，参与这些过程。在我们的研究中,Cxcr4的敲低抑制小鼠胚胎腭间充质（MEPM）细胞的迁移，类似于使用其抑制剂plerixafor，补充C-X-C基序趋化因子配体12（CXCL12）可以部分逆转Cxcr4敲除组的细胞迁移抑制作用。与低剂量视黄酸（RA）联合使用，plerixafor通过降低Cxcr4及其下游迁移调节基因Rac家族小GTP酶1（RAC1）介导肌动蛋白细胞骨架的表达来影响层状足形成和局灶性复合物组装以及ras同源蛋白家族成员A（RHOA）调节肌动蛋白细胞骨架以影响应力纤维形成和局灶性复合物成熟为局灶性粘连，从而增加了小鼠left裂的发生率。我们的结果表明，通过抑制Cxcr4表达破坏细胞迁移和破坏正常pal发育可能是通过Rac1与RhoA介导的。视黄酸和plerixafor联合使用可能会增加腭裂的发生率，这也提供了指导在受孕期间使用该药物的理由。
