Diffusional Landscapes for the Study of Neural Differentiation

在中枢神经系统的早期发育过程中，脊髓内化学物质的分布和浓度对神经元的分化和发育起着指导作用。脊髓内的化学成分和无数化学刺激物的浓度，既表明了将要发育的神经细胞的类型，也提供了“面包屑的踪迹”，以指导与其他神经元的精确突触连接。本研究提出了一个微系统，可以产生多种相关化学物质的特定浓度谱，以研究神经元的发育和分化。利用微纳米技术，一个微系统将被设计、制造、表征，并用于生成影响脊髓发育的已知化学物质的化学概况。将研究四种小鼠脊髓化学介质的选集：音hedgehog (Shh)，骨形态发生蛋白（BMP），视黄酸（RA）和noggin，并将由此产生的神经细胞的时空组织学分布映射到施加的化学介质浓度。这种方法的优点是可以在生物学相关的环境中研究细胞，而不需要引入体内发现的无数未知和不受控制的参数。该项目将支持缅因大学研究生和本科生的教育和实验室研究培训，这是一个涉及生物、微/纳米制造和仪器技术工程方法的多学科合作研究项目。该项目也将在缅因大学面向高中生的“考虑工程”暑期项目以及一些本科和研究生水平的课程中得到强调，以向科学和工程初学者介绍跨学科研究。微系统将在这些程序/课程中扩展，以涵盖以下应用：认知模型，人工智能，生物计算和神经网络。

During early development of the central nervous system, the global landscape and concentration of chemical species within the spinal cord serve to direct neuron differentiation and development. The chemical constituency and concentrations of myriad chemical stimulants within the spinal cord signals both the type of neural cells that will develop as well as provide a "trail of breadcrumbs" to direct the precise synaptic connections to other neurons. This research presents a microsystem that generates specific concentration profiles of multiply relevant chemical species to study the development and differentiation of neurons. Using micro and nanofabrication, a microsystem will be designed, fabricated, characterized, and used to generate chemical profiles of known chemicals that affect spinal cord development. An anthology of four mouse spinal cord chemical mediators will be studied: sonic hedgehog (Shh), bone morphogenic protein (BMP), retinoic acid (RA), and noggin, and the spatial and temporal histological distributions of resulting neural cells will be mapped to the imposed chemical mediator concentrations. The advantage of this approach is that cells can be studied in biologically relevant environments without the introduction of the myriad unknown and uncontrolled parameters found in vivo. This project will support the education and laboratory research training of both graduate and undergraduate students at the University of Maine in a collaborative, multi-disciplinary research project involving biological, micro/nano fabrication, and engineering methods in instrumentation and techniques. The project will also be highlighted in UMaine's "Consider Engineering" summer program for high school students and in several undergraduate and graduate level courses to introduce science & engineering initiates to interdisciplinary research. The microsystem will be extended within these programs/courses to encompass applications involving: cognition models, artificial intelligence, biocomputing, and neural networks.