Endochondral Potential of Trunk Neural Crest Cells

神经脊细胞(NCC)是外胚层来源的干细胞，可分化为丰富的 衍生品。高等脊椎动物头盖区的神经干细胞产生软骨和骨骼。 躯干神经干细胞在正常发育下不会生成骨骼或软骨，但它们可以 在体外诱导，或在实验中移植到特定的骨形成区域时 头盖骨。我们最近的研究表明，颅脑NCC的诱导发生在 原肠形成，比之前认为的要早得多(Basch等人)。2006)。此外，我们还发现了一个 不依赖于中胚层和神经组织的神经脊诱导机制。这些结果 背离当前神经脊线诱导的教条，为NCCS提供一个新的时间框架 发展。 这项建议的目的是确定控制软骨生成的分子原理。 分化潜能的研究。这种对脊椎动物发育至关重要的干细胞。我们建议 通过移植策略挑战树干神经干细胞的骨和软骨潜力，以证明 早期诱导信号的作用。然后我们将测试尾化信号的效果(成纤维细胞生长因子和 WNT)在躯干和颅骨NCC的成软骨分化潜能中。

Neural crest cells (NCCs) are ectodermally derived stem cells that differentiate into a wealth of derivatives. NCCs from the cranial region of higher vertebrates generate cartilage and bone. Trunk NCCs don't generate bone or cartilage under normal development, but they can be induced to do so in vitro, or when experimentally grafted in specific bone forming territories of the cranium. We have recently shown that the induction of cranial NCCs occurs during gastrulation, much earlier than previously thought (Basch et al. 2006). Additionally we uncover a neural crest induction mechanism independent of mesodermal and neural tissues. These results depart from current dogmas of neural crest induction and provide a new timeframe for NCCs development. The aim of this proposal is to identify the molecular principles governing the chondrogenic differentiation potential of. this critical stem cell for vertebrate development. We propose to challenge the bone and cartilage potential of trunk NCCs through grafting strategies to prove the role of early signals of induction. Then we will test the effects of caudalizing signals (FGF and Wnt) in the chondrogenic differentiation potential of both trunk and cranial NCC.