Patterning, morphogenesis and differentiation of embryos

受精后，卵子分裂形成多细胞胚胎。胚胎通过形态发生过程和细胞分化而组织成一个复杂的身体，由具有特殊组织的器官组成。胚胎的细胞获得与它们在胚胎中的位置相适应的特殊命运，然后分化。这种命运的指定是模式事件的结果，模式事件取决于卵子发生期间施加的卵子组织，以及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依赖于它们与细胞表面和细胞外基质中复杂的硫化蛋白多糖的相互作用。我们将在一个简单的海洋胚胎(海胆)中研究这些事件，这种胚胎在许多方面都像哺乳动物的胚胎一样发育。它在海水中外部生长，是透明的，允许显微镜检查和实验干预。我们发现，实验上抑制硫酸化蛋白多糖的形成会破坏这些胚胎的图案以及一些形态发生事件，特别是原肠形成和嘴的形成。我们正在利用从最近测序的海胆基因组中获得的信息，通过下调参与蛋白多糖形成和修饰的基因的表达，更好地了解硫酸蛋白多糖的作用。我们推测，Nodal的自动调节信号是建立和维持口腔-流产(腹侧-背部)轴和完成原肠形成所必需的，并且Nodal依赖于它可能与其结合的硫化蛋白多糖的相互作用。我们还将研究高等脊椎动物中涉及视觉和听觉的基因在海胆胚胎和幼虫中的表达和可能的作用。令人惊讶的是，在海胆基因组中发现了这些基因，其中包括哺乳动物视网膜形成所需的一些基因和人类的亚瑟综合症基因，其中许多基因在胚胎(没有眼睛和耳朵)中表达。

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).