Isolation and Characterization of Neural Crest Subpopulation

这个项目将从美国国家科学基金会资助的第十年开始，解决发育生物学中的一个关键问题：再生障碍性贫血是如何由相对较少的胚胎细胞产生组成个体的多种细胞类型的？一个可以解决这个问题的理想模型系统是神经脊，它在所有脊椎动物物种的发育早期就出现了。虽然神经脊在发育过程中只有几天的时间可以识别，但它在身体中产生了无数重要的结构。在数百种神经脊衍生物中，有整个外周神经系统，皮肤中的所有色素细胞，以及牙齿中形成牙本质的细胞。在一个正常人身上，这么多不同类型的细胞是如何从看似相同的细胞群体中构成的？在之前NSF的支持下，该实验室设计了复杂的细胞分选技术来分离和研究神经脊细胞亚群。此外，他们可以移植神经脊细胞，并在整个发育过程中跟踪移植的细胞。目前的研究将通过检测移植后两个已识别的亚群的发展来具体检查单个神经细胞类型是如何从神经脊产生的。本课程将研究将明显同质的神经脊细胞定向为特定神经元的事件，并将识别与这些事件相关的特定控制基因。这些研究处于细胞和分子生物学的交界处，这是第一次有可能解决发育神经科学中最基本的问题之一。

This project, which will begin its tenth year of support from the NSF, addresses one of the critical questions in developmental biology: how do aa relatively small number of embryonic cells give rise to the multitude of cell types that make up the individual? An ideal model system in which this question can be addressed is the neural crest, which appears very early in the development in all vertebrate species. Although the neural crest is only recognizable for a few days during the course of development, it gives rise to a myriad of important structures in the body. Among the hundreds of neural crest derivatives is the entire peripheral nervous system, all of the pigment cells in the skin and the cells that make the dentin in the teeth. How are such an enormous number of diverse cell types made from a seemingly homogeneous population of cells in a normal individual? With previous NSF support, this laboratory devised sophisticated cell sorting techniques for isolating and studying subpopulations of neural crest cells. Furthermore, they can transplant neural crest cells and follow the transplanted cells throughout development. The current studies will specifically examine how individual neuronal cell types arise from the neural crest by examining the development of two identified subpopulations following transplantation. The events that direct apparently homogeneous neural crest cells to become specific neurons will be examined, and the specific control genes that are associated with these events will be identified. These studies are at the interface of cellular and molecular biology, where, for the first time, it is now possible to address one of the most fundamental questions in developmental neuroscience.