Semaphorin 3d promotes cell proliferation and neural crest cell development downstream of TCF in the zebrafish hindbrain

Semaphorin 3d promotes cell proliferation and neural crest cell development downstream of TCF in the zebrafish hindbrain
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DOI:
10.1242/dev.02583
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发表时间:
2006-10-15
期刊:
影响因子:
4.6
通讯作者:
Halloran, Mary C.
Halloran, Mary C.
中科院分区:
生物学2区
文献类型:
--
作者:
Berndt, Jason D.;Halloran, Mary C.

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神经嵴细胞(NCC)是多能迁移细胞,对周围神经系统、色素细胞、颅面软骨和骨的发育至关重要。NCC在背外胚层内被指定,并经历上皮向间充质转化(EMT),以便迁移到它们分化的靶目的地。在这里,我们报告的作用,神经细胞癌的发展中的脑信号蛋白家族的细胞导向分子的成员。吗啉代介导的Sema 3d敲低抑制后脑神经上皮细胞增殖此外,Sema 3d敲低减少了迁移性NCC的标志物并破坏了NCC衍生的组织。类似地,TCF的显性-阻遏物形式(Delta TCF)的表达降低后脑细胞增殖并导致迁移性NCC标志物的破坏。此外,Delta TCF的表达下调sema 3d RNA的表达。最后,Sema 3d过表达挽救了由Delta TCF表达引起的增殖减少,表明Sema 3d位于被认为控制NCC前体细胞周期的分子途径中的Wnt/TCF信号传导的下游。
Neural crest cells (NCCs) are pluripotent migratory cells that are crucial to the development of the peripheral nervous system, pigment cells and craniofacial cartilage and bone. NCCs are specified within the dorsal ectoderm and undergo an epithelial to mesenchymal transition (EMT) in order to migrate to target destinations where they differentiate. Here we report a role for a member of the semaphorin family of cell guidance molecules in NCC development. Morpholino-mediated knockdown of Sema3d inhibits the proliferation of hindbrain neuroepithelial cells. In addition, Sema3d knockdown reduces markers of migratory NCCs and disrupts NCC-derived tissues. Similarly, expression of a dominant-repressor form of TCF (Delta TCF) reduces hindbrain cell proliferation and leads to a disruption of migratory NCC markers. Moreover, expression of Delta TCF downregulates sema3d RNA expression. Finally, Sema3d overexpression rescues reduced proliferation caused by Delta TCF expression, suggesting that Sema3d lies downstream of Wnt/TCF signaling in the molecular pathway thought to control cell cycle in NCC precursors.