Greene Robert M, Pisano M Michele
Department of Molecular, Cellular and Craniofacial Biology, University of Louisville, Birth Defects Center, ULSD, Louisville, Kentucky 40292, USA.
Birth Defects Res C Embryo Today. 2010 Jun;90(2):133-54. doi: 10.1002/bdrc.20180.
In the past, most scientists conducted their inquiries of nature via inductivism, the patient accumulation of "pieces of information" in the pious hope that the sum of the parts would clarify the whole. Increasingly, modern biology employs the tools of bioinformatics and systems biology in attempts to reveal the "big picture." Most successful laboratories engaged in the pursuit of the secrets of embryonic development, particularly those whose research focus is craniofacial development, pursue a middle road where research efforts embrace, rather than abandon, what some have called the "pedestrian" qualities of inductivism, while increasingly employing modern data mining technologies. The secondary palate has provided an excellent paradigm that has enabled examination of a wide variety of developmental processes. Examination of cellular signal transduction, as it directs embryogenesis, has proven exceptionally revealing with regard to clarification of the "facts" of palatal ontogeny-at least the facts as we currently understand them. Herein, we review the most basic fundamentals of orofacial embryology and discuss how functioning of TGFbeta, BMP, Shh, and Wnt signal transduction pathways contributes to palatal morphogenesis. Our current understanding of palate medial edge epithelial differentiation is also examined. We conclude with a discussion of how the rapidly expanding field of epigenetics, particularly regulation of gene expression by miRNAs and DNA methylation, is critical to control of cell and tissue differentiation, and how examination of these epigenetic processes has already begun to provide a better understanding of, and greater appreciation for, the complexities of palatal morphogenesis.
过去,大多数科学家通过归纳法来探究自然,即耐心地积累“一条条信息”,虔诚地希望这些部分的总和能阐明整体。如今,现代生物学越来越多地运用生物信息学和系统生物学工具,试图揭示“全貌”。大多数致力于探寻胚胎发育奥秘的成功实验室,尤其是那些专注于颅面发育研究的实验室,走的是一条中间道路:他们的研究工作既不摒弃、反而接纳了一些人所谓归纳法的“平淡无奇”之处,同时也越来越多地运用现代数据挖掘技术。次生腭提供了一个绝佳的范例,可用于研究各种各样的发育过程。研究指导胚胎发生的细胞信号转导,已被证明在阐明腭个体发生的“事实”方面极具启发性——至少是就我们目前所理解的事实而言。在此,我们回顾口腔颌面胚胎学的最基本原理,并讨论转化生长因子β(TGFbeta)信号转导通路、骨形态发生蛋白(BMP)信号转导通路、音猬因子(Shh)信号转导通路和Wnt信号转导通路如何促进腭的形态发生。我们还将审视目前对腭内侧边缘上皮分化的理解。最后,我们将讨论表观遗传学这一迅速发展的领域,特别是微小RNA(miRNAs)和DNA甲基化对基因表达的调控,如何对细胞和组织分化的控制至关重要,以及对这些表观遗传过程进行研究如何已经开始让我们更好地理解腭形态发生的复杂性,并对其复杂性有更深的认识。