Differential regulation of specification and subsequent migration of neural crest progenitors

神经嵴祖细胞规格和随后迁移的差异调节

• 批准号: 209911085
• 负责人: Professor Dr. Klaus Unsicker
• 金额: --
• 依托单位: Department of Medical Neurobiology
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/209911085?language=en
• 关键词: Differential; regulation; specification; subsequent; migration

In the trunk of avian embryos, neural crest (NC) cells successively delaminate from the neural tube (NT) for over two days. We recently uncovered that the dorsal NT is a dynamic region traversed sequentially by progenitors that colonize NC derivatives in a ventral to dorsal order (sympathetic ganglia, then Schwann cells, DRG and finally melanocytes). Hence, a dynamic spatio-temporal fate map is present already within the NT. Furthermore, we documented that premigratory cells are already restricted to generate single derivatives. What are the signals imparted by the dorsal NT compared to those provided by the migratory environment and what are their precise functions? What is the relationship between cell specification and control of subsequent migration, i.e; does the state of specification of a cell convey the receptor repertoire for precise migration and homing, or are these distinctly regulated events?. To tackle these fundamental questions, we will use two extreme paradigms, the development of the sympathetic and of the melanocyte lineages, the first and last progenitors to emigrate from the NT, and that migrate differentially along ventral vs. lateral pathways, respectively. Experiments will be performed in avian embryos using in vivo approaches in combination with molecular, microsurgical, immunohistochemical and electron microscopical techniques. Loss and gain of gene function will be executed using the tet-on/tet-off system to achieve precise spatio-temporal resolution. These studies will be significant for understanding how hierarchical decisions during neural development cooperate with pathfinding cues to allow differentiation only at the appropriate primordia.

在鸟类胚胎的躯干中，神经嵴（NC）细胞连续从神经管（NT）剥离2天以上。我们最近发现，NT背侧是一个动态区域，由NC衍生物的祖细胞按腹侧到背侧顺序依次迁移（交感神经节，然后是雪旺细胞，DRG，最后是黑素细胞）。因此，一个动态的时空命运图已经存在于NT中。此外，我们记录了前迁移细胞已经局限于产生单一衍生物。与迁徙环境提供的信号相比，北侧背侧传递的信号是什么？它们的确切功能是什么？细胞规格与后续迁移控制之间的关系是什么？细胞的特定状态是否传达了精确迁移和归巢的受体库，或者这些是明显受调节的事件？为了解决这些基本问题，我们将使用两个极端的范例，交感细胞和黑素细胞谱系的发展，从NT迁移的第一个和最后一个祖细胞，以及分别沿腹侧和外侧途径迁移的差异。实验将在禽类胚胎中进行，采用分子、显微外科、免疫组织化学和电子显微镜技术相结合的体内方法。基因功能的丧失和获得将使用测试/测试系统来执行，以实现精确的时空分辨率。这些研究对于理解神经发育过程中的层次决策如何与寻径线索合作，仅在适当的原基上允许分化具有重要意义。

项目成果

MiR-124 is differentially expressed in derivatives of the sympathoadrenal cell lineage and promotes neurite elongation in chromaffin cells

• DOI: 10.1007/s00441-016-2395-9
• 发表时间: 2016-04
• 期刊: Cell and Tissue Research
• 影响因子: 3.6
• 作者: Stella Shtukmaster;Priyanka Narasimhan;Tehani El Faitwri;J. Stubbusch;U. Ernsberger;H. Rohrer;K. Unsicker;K. Huber