ANTEROPOSTERIOR ECTODERMAL PATTERNING IN XENOPUS

非洲爪蟾的前后外胚层模式

• 批准号: 6697308
• 负责人: Hazel L Sive
• 金额: $ 38.48万
• 依托单位: WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6697308
• 关键词: ANTEROPOSTERIOR; ECTODERMAL; PATTERNING; XENOPUS

DESCRIPTION (provided by applicant): The long-term goals of this project are to understand the molecular mechanisms responsible for determination and patterning of the presumptive neurectoderm (dorsal ectoderm) of the frog Xenopus laevis. The goals of this proposal are to ask how the neurectoderm is first set aside, by exploring how expression of a marker gene is restricted to the presumptive neurectoderm. In a subtractive cloning screen to define very early markers of neural pattern, the Sive lab isolated opl, which encodes a zinc finger protein, a member of the zic gene family. Opl is expressed throughout the presumptive neurectoderm during gastrulation. In ectodermal explants, opl expression can be activated by the Bone Morphogenetic Protein (BMP) antagonist Noggin and by Wnt3a. We will connect the activities of the secreted factors Noggin and Wnt3a with activation of opl expression. Although BMP antagonists have been strongly implicated in neural determination in Xenopus, the mechanism by which removal of BMPs activates downstream genes is not understood. Similarly, Wnt proteins are implicated in posterior neural patterning and general neural determination, but the mechanism by which they activate neurectodermal target genes may be complex. Regions of the opl promoter responsive to Noggin and to Wnt3a have been defined in explants. These sequences will be further analyzed and compared to those required to restrict opl expression to the neural plate of transgenic embryos. A factor(s), which interacts with the Noggin-responsive element will be identified. Phylogenetically conserved elements in the opI promoter will be defined. Many birth defects affect the neural tube, however their genetic cause is generally not understood. This proposal will define normal developmental mechanisms and therefore give insight into causes of abnormal development. The mechanisms through which signal transduction pathways change expression of neurectodermal target genes is poorly understood, and abnormal responses to signaling molecules play a role in multiple diseases, including cancers. This proposal will help define mechanisms by which abnormal response to a signaling event is elicited.

描述（由申请人提供）：该项目的长期目标是了解负责确定和模式化非洲爪蟾推定神经外胚层（背侧外胚层）的分子机制。该提案的目标是通过探索标记基因的表达如何限制在假定的神经外胚层中，来询问神经外胚层是如何首先被搁置的。在定义神经模式早期标记的消减克隆筛选中，Sive 实验室分离出了 opl，它编码锌指蛋白（zic 基因家族的成员）。原肠胚形成期间，Opl 在整个假定的神经外胚层中表达。在外胚层外植体中，opl 表达可由骨形态发生蛋白 (BMP) 拮抗剂 Noggin 和 Wnt3a 激活。我们将分泌因子 Noggin 和 Wnt3a 的活动与 opl 表达的激活联系起来。 尽管 BMP 拮抗剂与非洲爪蟾的神经决定密切相关，但去除 BMP 激活下游基因的机制尚不清楚。类似地，Wnt 蛋白与后神经模式和一般神经决定有关，但它们激活神经外胚层靶基因的机制可能很复杂。已在外植体中定义了对 Noggin 和 Wnt3a 敏感的 opl 启动子区域。这些序列将被进一步分析并与限制 opl 表达至转基因胚胎神经板所需的序列进行比较。将识别与 Noggin 响应元件相互作用的因子。 opI 启动子中系统发育保守的元件将被定义。许多出生缺陷会影响神经管，但其遗传原因通常尚不清楚。该提案将定义正常的发育机制，从而深入了解异常发育的原因。人们对信号转导途径改变神经外胚层靶基因表达的机制知之甚少，对信号分子的异常反应在包括癌症在内的多种疾病中发挥着作用。该提案将有助于定义引发对信令事件的异常响应的机制。