Developmental Mechanisms of Neurogenesis

神经发生的发育机制

• 批准号: RGPIN-2016-03737
• 负责人: Burke, Robert
• 金额: $ 3.21万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=688774
• 关键词: Developmental; Mechanisms; Neurogenesis

Most of what we know about the embryonic development of nervous systems comes from studies of flies or mice. As those studies revealed similar signaling systems and molecular pathways, it was proposed that nervous systems arose once, early in the history of multicellular animals. Subsequent studies in several types of invertebrates support this idea, but the striking diversity in how nervous systems develop makes it difficult to rationalize a single origin. A more refined explanation is that there has been independent evolution of the cellular organization in many groups and neurogenesis has drawn upon conserved signaling systems and molecular pathways in various ways as animals diversified. We lack the models necessary to test this hypothesis, as the molecular and cellular mechanisms underlying neurogenesis need to be carefully analyzed to make useful comparisons in groups of related animals. ** Deuterostomes are a large grouping of animals including vertebrates and several invertebrates groups that are closely related by measurements of molecular kinship, yet have very diverse body forms. The organization of nervous systems within the deuterostomes ranges from simple to very complex. To better understand the origin and diversification of multicellular animals I have developed a research program with the long-term objective of determining the cellular and molecular mechanisms of neurogenesis in sea urchin embryos. These studies will establish a novel neurogenesis model and provide new insights into metazoan evolution. Sea urchins are echinoderms, one of the basal groups of deuterostomes, so mechanisms they employ in neurogenesis reveal fundamental features shared by all deuterostomes, and those that have arisen in more complex deuterostomes. Sea urchins have been used for 150 years to study many aspects of early development. Excellent genomic resources, simple systems for controlling gene expression, and clear embryos, conducive to imaging, make sea urchins excellent models. The proposed studies will examine dedicated neural progenitors, or neural stem cells. It will determine how Notch signaling and fibroblast growth factor (FGF) signaling function in neurogenesis. As well, it will determine if the central nervous system is patterned, or expresses certain transcription factors and has dedicated neural progenitors in specific anatomical locations. The research will use novel methods and will generate unique reagents to further use of this model. The proposed studies are excellent projects for students, and the training gives highly desired skills that ensure their further success. This research will have broad impact across disciplines, because understanding the cellular and molecular mechanisms by which embryonic cells are transformed into a complex nervous system is relevant to developmental biology, neurobiology, evolutionary biology, cell, and molecular biology. ****

我们对神经系统的胚胎发育的了解中的大多数来自对苍蝇或小鼠的研究。 正如这些研究揭示了相似的信号系统和分子途径的那样，有人提出，在多细胞动物史的早期，神经系统曾经出现一次。 随后对几种无脊椎动物的研究支持了这一想法，但是神经系统发展方式的惊人多样性使得很难合理化单个起源。 一个更精致的解释是，在许多群体中，细胞组织已经独立演变，随着动物的多样化，神经发生以各种方式吸引了保守的信号传导系统和分子途径。 我们缺乏检验该假设所需的模型，因为需要仔细分析神经发生的分子和细胞机制，以便在相关动物组中进行有用的比较。 **氘抑制是大量的动物分组，包括脊椎动物和几个无脊椎动物组，它们通过测量分子亲属关系密切相关，但具有非常多样化的身体形式。神经系统内的神经系统的组织范围从简单到非常复杂。为了更好地了解多细胞动物的起源和多样化，我已经开发了一项研究计划，其长期目标是确定海胆胚胎中神经发生的细胞和分子机制。 这些研究将建立一种新型的神经发生模型，并为后生动物进化提供新的见解。 海胆是棘皮动物，是氘抑制的基础组之一，因此它们在神经发生中采用的机制揭示了所有氘代表的基本特征，以及在更复杂的氘核静脉体中产生的那些机制。海胆已有150年来研究早期发展的许多方面。 优秀的基因组资源，用于控制基因表达的简单系统以及有利于成像的清晰胚胎，使海胆良好的模型。拟议的研究将检查专用的神经祖细胞或神经干细胞。 它将决定神经发生中的Notch信号传导和成纤维细胞生长因子（FGF）信号传导功能。同样，它将确定中枢神经系统是图案化的，还是表达某些转录因子，并在特定的解剖学位置具有专门的神经祖细胞。 该研究将使用新颖的方法，并将生成独特的试剂以进一步使用该模型。拟议的研究是学生的出色项目，培训提供了高度理想的技能，以确保其进一步的成功。这项研究将在各学科中产生广泛的影响，因为了解将胚胎细胞转化为复杂神经系统的细胞和分子机制与发育生物学，神经生物学，进化生物学，细胞和分子生物学有关。 ****