Pax3 and Zic1 drive induction and differentiation of multipotent, migratory, and functional neural crest in Xenopus embryos
Pax3 and Zic1 drive induction and differentiation of multipotent, migratory, and functional neural crest in Xenopus embryos
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DOI：
10.1073/pnas.1219124110
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发表时间：
2013-04-02
影响因子：
11.1
通讯作者：
Monsoro-Burq, Anne Helene
中科院分区：
文献类型：
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作者：
Milet, Cecile;Maczkowiak, Frederique;Monsoro-Burq, Anne Helene
在众多候选基因中，确定哪些关键因素控制胚胎谱系的承诺是发育生物学中一个长期存在的挑战，也是开发基于干细胞的疗法的必要前提。承诺意味着诱导细胞不仅表达早期谱系标记，而且进一步经历自主分化成谱系。胚胎神经嵴产生高度多样化的衍生物，包括黑素细胞、神经元、神经胶质、软骨、间质和骨。一个复杂的基因调控网络最近对参与神经嵴诱导、规范、迁移和分化的许多步骤的基因进行了分类。然而，哪些因素或因素组合足以触发这种多能谱系的完全承诺仍然未知。在这里，我们表明，与其他潜在的候选因子组合相比，共激活转录因子Pax3和Zic1不仅可以启动爪蟾和鸡胚胎各种早期胚胎谱系的神经嵴形成，还可以触发完整的神经嵴形成。这两个因素足以驱动几种神经嵴衍生物在体外或体内异位的最小培养条件下的迁移和分化。移植后，诱导细胞迁移并融入正常神经嵴颅面靶区，表明在体内具有有效的空间识别能力。因此，Pax3和Zic1合作并执行转录开关，足以激活完整的多能神经嵴发育和分化。
Defining which key factors control commitment of an embryonic lineage among a myriad of candidates is a longstanding challenge in developmental biology and an essential prerequisite for developing stem cell-based therapies. Commitment implies that the induced cells not only express early lineage markers but further undergo an autonomous differentiation into the lineage. The embryonic neural crest generates a highly diverse array of derivatives, including melanocytes, neurons, glia, cartilage, mesenchyme, and bone. A complex gene regulatory network has recently classified genes involved in the many steps of neural crest induction, specification, migration, and differentiation. However, which factor or combination of factors is sufficient to trigger full commitment of this multipotent lineage remains unknown. Here, we show that, in contrast to other potential combinations of candidate factors, coactivating transcription factors Pax3 and Zic1 not only initiate neural crest specification from various early embryonic lineages in Xenopus and chicken embryos but also trigger full neural crest determination. These two factors are sufficient to drive migration and differentiation of several neural crest derivatives in minimal culture conditions in vitro or ectopic locations in vivo. After transplantation, the induced cells migrate to and integrate into normal neural crest craniofacial target territories, indicating an efficient spatial recognition in vivo. Thus, Pax3 and Zic1 cooperate and execute a transcriptional switch sufficient to activate full multipotent neural crest development and differentiation.