Patterning, morphogenesis and differentiation of embryos

胚胎的模式、形态发生和分化

• 批准号: 45977-2008
• 负责人: Brandhorst, Bruce
• 金额: $ 3.28万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=513521
• 关键词: Patterning; morphogenesis; differentiation; embryos

After fertilization an egg cleaves to form a multi-cellular embryo. The embryo becomes organized via morphogenetic processes and cellular differentiation into a complex body consisting of organs having specialized tissues. The cells of the embryo acquire specialized fates appropriate for their position in the embryo and then differentiate. This specification of fates is the result of patterning events that depend on the organization of the egg imposed during oogenesis and on cellular interactions that involve intercellular signalling molecules and their receptors. The activities of many of these signalling molecules depend on their interactions with complex sulfated proteoglycans on the surface of cells and in the extra-cellular matrix. We will investigate these events in a simple marine embryo (the sea urchin), which in many ways develops like mammalian embryos. It develops externally in sea water and is transparent, allowing microscopy examination and experimental interventions. We have found that experimental inhibition of the formation of sulfated proteoglycans disrupts the patterning of these embryos as well as some morphogenetic events, gastrulation and mouth formation in particular. We are taking advantage of information derived from the recently sequenced genome of the sea urchin to gain a better understanding of the role of sulphated proteoglycans by knocking down the expression of genes involved in their formation and modification. We hypothesize that auto-regulatory signalling by Nodal is required for establishment and maintenance of the oral-aboral (ventral-dorsal) axis and completion of gastrulation and that Nodal depends on interactions with sulfated proteoglycans to which it probably binds. We will also investigate the expression and possible roles in sea urchin embryos and larvae of genes involved in vision and hearing in higher vertebrates. These genes, including some required for retina formation in mammals and the genes of the Usher syndrome in humans, were surprisingly found in the sea urchin genome and many are expressed in embryos (which lack eyes and ears).

受精后卵裂形成多细胞胚胎。胚胎通过形态发生过程和细胞分化形成一个复杂的身体，由具有专门组织的器官组成。胚胎细胞获得适合于它们在胚胎中的位置的特殊命运，然后分化。这种命运的规范是模式事件的结果，这些事件依赖于卵发生过程中施加的卵子组织和涉及细胞间信号分子及其受体的细胞相互作用。许多这些信号分子的活性取决于它们与细胞表面和细胞外基质中的复杂硫酸化蛋白聚糖的相互作用。我们将在一个简单的海洋胚胎（海胆）中研究这些事件，它在许多方面像哺乳动物胚胎一样发育。它在海水外部发育，是透明的，允许显微镜检查和实验干预。我们发现，对硫酸盐蛋白聚糖形成的实验抑制破坏了这些胚胎的模式以及一些形态发生事件，特别是原肠胚形成和口的形成。我们正在利用最近对海胆基因组测序的信息，通过敲低硫酸盐蛋白聚糖形成和修饰相关基因的表达，来更好地了解硫酸盐蛋白聚糖的作用。我们假设Nodal的自动调节信号是建立和维持口-口（腹-背）轴和完成原肠形成所必需的，并且Nodal依赖于与它可能结合的硫酸化蛋白聚糖的相互作用。我们还将研究高等脊椎动物中与视觉和听觉有关的基因在海胆胚胎和幼虫中的表达及其可能的作用。令人惊讶的是，这些基因，包括哺乳动物视网膜形成所需的一些基因和人类Usher综合征的基因，在海胆基因组中被发现，许多基因在胚胎（没有眼睛和耳朵）中表达。