Demers Christopher J, Soundararajan Prabakaran, Chennampally Phaneendra, Cox Gregory A, Briscoe James, Collins Scott D, Smith Rosemary L
Microinstruments and Systems Laboratory, University of Maine, Orono, ME 04469, USA Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
Moffitt Cancer Center, Tampa, FL 33612, USA.
Development. 2016 Jun 1;143(11):1884-92. doi: 10.1242/dev.126847.
Embryogenesis is a highly regulated process in which the precise spatial and temporal release of soluble cues directs differentiation of multipotent stem cells into discrete populations of specialized adult cell types. In the spinal cord, neural progenitor cells are directed to differentiate into adult neurons through the action of mediators released from nearby organizing centers, such as the floor plate and paraxial mesoderm. These signals combine to create spatiotemporal diffusional landscapes that precisely regulate the development of the central nervous system (CNS). Currently, in vivo and ex vivo studies of these signaling factors present some inherent ambiguity. In vitro methods are preferred for their enhanced experimental clarity but often lack the technical sophistication required for biological realism. In this article, we present a versatile microfluidic platform capable of mimicking the spatial and temporal chemical environments found in vivo during neural tube development. Simultaneous opposing and/or orthogonal gradients of developmental morphogens can be maintained, resulting in neural tube patterning analogous to that observed in vivo.
胚胎发生是一个高度受调控的过程，在此过程中，可溶性信号的精确时空释放引导多能干细胞分化为离散的成年特化细胞类型群体。在脊髓中，神经祖细胞通过从附近组织中心（如底板和近轴中胚层）释放的介质作用，被引导分化为成年神经元。这些信号共同作用，形成时空扩散格局，精确调控中枢神经系统（CNS）的发育。目前，对这些信号因子的体内和体外研究存在一些内在的模糊性。体外方法因其增强的实验清晰度而更受青睐，但往往缺乏生物学真实性所需的技术复杂性。在本文中，我们展示了一个多功能微流控平台，该平台能够模拟神经管发育过程中体内发现的时空化学环境。可以维持发育形态发生素的同时相反和/或正交梯度，从而产生类似于体内观察到的神经管模式。
