Isolation and Characterization of Neural Crest Subpopulation

这个项目将在获得美国国家科学基金会（NSF）支持的第十个年头开始，它解决了发育生物学中的一个关键问题：相对少量的胚胎细胞是如何产生构成个体的大量细胞类型的？可以解决这个问题的理想模型系统是神经嵴，它在所有脊椎动物物种的发育中都很早就出现了。虽然在发育过程中，神经嵴只能在几天内被识别出来，但它在体内产生了无数重要的结构。在数百个神经嵴衍生物中，有整个周围神经系统，皮肤中的所有色素细胞和牙齿中形成牙本质的细胞。一个正常人体内看似同质的细胞群是如何产生如此多的不同细胞类型的呢？在以前的国家科学基金会的支持下，该实验室设计了复杂的细胞分选技术，用于分离和研究神经嵴细胞亚群。此外，他们可以移植神经嵴细胞，并在整个发育过程中跟踪移植细胞。目前的研究将通过检查移植后两个确定的亚群的发展，专门研究单个神经元细胞类型如何从神经嵴产生。我们将研究导致表面上同质的神经嵴细胞转变为特定神经元的事件，并确定与这些事件相关的特定控制基因。这些研究处于细胞生物学和分子生物学的交叉点，在那里，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.