Plasticity and Regulation in Xenopus Anterior-Posterior Patterning

非洲爪蟾前后图案的可塑性和调节

基本信息

批准号：
8580604
负责人：
MARGARET S SAHA
金额：
$ 36.75万
依托单位：
COLLEGE OF WILLIAM AND MARY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8580604
关键词：
Address Amphibia Anterior Back Behavior Candidate Disease Gene Characteristics Data Development Developmental Biology Disease Educational process of instructing Embryo Embryonic Development Ensure Environment Event FGF8 gene Gastrula Geminin Gene Expression Gene Expression Profile Gene Expression Profiling Genes Genetic Goals Knowledge Lead Light Mediating Microarray Analysis Molecular Molecular Profiling Nervous system structure Neuronal Plasticity Neurons Organism Pathway interactions Pattern Process Regenerative Medicine Regulation Risk Rotation Signal Transduction Signaling Molecule Sorting - Cell Movement Specificity Staging Stem cells Students System Techniques Time Tissue Donors Tissue Engineering Tissues Transplantation Work Xenopus Xenopus laevis body system cell type cellular engineering knock-down neural plate novel public health relevance relating to nervous system research study restoration transcriptome sequencing undergraduate student

项目摘要

DESCRIPTION (provided by applicant): The development of a functional organ system not only entails the determinative events that lead to cell type specificity and appropriate patterning of those cell types, but also the ability to maintain this identity and pattern in the face of geneic and environmental perturbations that occur throughout embryogenesis. This ability to compensate for potentially disruptive alterations in development, which is often referred to regulation, is a near-universal characteristic of embryos, one that is required to ensure normal development. However, there has been relatively little focus on elucidating the mechanisms governing the process of regulation following a developmental perturbation, despite its clear importance for a complete understanding of development as well as its implications for regenerative medicine. Here we employ the classic amphibian embryological system of Xenopus laevis to examine regulative ability during early embryogenesis. Previous experiments from our lab have demonstrated that when the presumptive neural plate is removed from a gastrula-stage embryo, rotated 180o, and transplanted back into a host embryo from which the equivalent region was removed, there is a near total regulation, with the resulting embryo giving rise to a nervous system with appropriate regional gene expression and functional capabilities. The overall goal of this proposal is to examine the mechanisms governing this profound regulative ability. The first specific aim will assess the temporal and spatial expression profile f candidate genes important for the process of regulation, with the goal of obtaining baseline information to determine precisely when and how this regulative process occurs. These genes include: regional markers (XCG-1, Otx-2, En-2, Krox-20, HoxB9); later differentiation genes (GAD, xvGlut1); genes expressed earlier in the neural determination pathway (FoxD5, Geminin, Sox2); and genes encoding key anterior-posterior signaling molecules (Frzb-1, xWnt8, and FGF8). The second aim will determine if specific signaling cascades mediate the process of regulation by perturbing their function using a targeted morpholino knockdown approach. Finally, unbiased global gene expression approaches, specifically microarray analysis and an RNA-seq approach, will identify additional molecular components of the regulation process. Taken together, the experiments proposed in these three aims will engage an eager cadre of undergraduate students at all levels in an effort to address a fundamental and poorly studied problem in developmental biology that has broader implications for regenerative medicine.

描述（由申请人提供）：功能器官系统的发育不仅需要导致细胞类型特异性和适当模式的决定性事件这些细胞类型的能力，而且在面对整个胚胎发生过程中发生的基因和环境扰动时保持这种身份和模式的能力。这种补偿发育过程中潜在破坏性改变的能力（通常称为调节）是胚胎的近乎普遍特征，也是确保正常发育所必需的。然而，尽管阐明发育扰动后的调节过程的机制对于全面理解发育及其对再生医学的影响具有明显的重要性，但相对较少的关注。在这里，我们利用非洲爪蟾的经典两栖动物胚胎系统来检查早期胚胎发生过程中的调节能力。我们实验室之前的实验已经证明，当从原肠胚阶段胚胎中取出假定的神经板，旋转 180°，然后移植回去除了等效区域的宿主胚胎中时，会产生近乎完全的调节，从而产生胚胎产生具有适当区域基因表达和功能能力的神经系统。该提案的总体目标是研究管理这种深刻调节能力的机制。第一个具体目标将评估对调节过程重要的候选基因的时间和空间表达谱，目的是获得基线信息以准确确定该调节过程何时以及如何发生。这些基因包括：区域标记（XCG-1、Otx-2、En-2、Krox-20、HoxB9）；后期分化基因（GAD、xvGlut1）；神经决定通路早期表达的基因（FoxD5、Geminin、Sox2）；以及编码关键前后信号分子（Frzb-1、xWnt8 和 FGF8）的基因。第二个目标将确定特定的信号级联是否通过使用靶向吗啉敲除方法扰乱其功能来介导调节过程。最后，公正的全局基因表达方法，特别是微阵列分析和RNA-seq方法，将识别调控过程的其他分子成分。总而言之，这三个目标中提出的实验将吸引各级本科生的热情参与，努力解决发育生物学中一个基本且研究不足的问题，该问题对再生医学具有更广泛的影响。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Expression of trpv channels during Xenopus laevis embryogenesis.

非洲爪蟾胚胎发生过程中 trpv 通道的表达。

DOI：
发表时间：
2018-12
期刊：
影响因子：
0
作者：
Dong, Chen;Paudel, Sudip;Amoh, Nana Yaa;Saha, Margaret S
通讯作者：
Saha, Margaret S

Dissection and downstream analysis of zebra finch embryos at early stages of development.

发育早期阶段斑胸草雀胚胎的解剖和下游分析。

DOI：
发表时间：
2014-06-21
期刊：
影响因子：
0
作者：
Murray, Jessica R;Stanciauskas, Monika E;Aralere, Tejas S;Saha, Margaret S
通讯作者：
Saha, Margaret S

A Markovian Entropy Measure for the Analysis of Calcium Activity Time Series.

用于分析钙活动时间序列的马尔可夫熵度量。

DOI：
发表时间：
2016
期刊：
影响因子：
3.7
作者：
Marken, John P;Halleran, Andrew D;Rahman, Atiqur;Odorizzi, Laura;LeFew, Michael C;Golino, Caroline A;Kemper, Peter;Saha, Margaret S
通讯作者：
Saha, Margaret S

The role of voltage-gated calcium channels in neurotransmitter phenotype specification: Coexpression and functional analysis in Xenopus laevis.

电压门控钙通道在神经递质表型规范中的作用：非洲爪蟾的共表达和功能分析。

DOI：
发表时间：
2014-08-01
期刊：
影响因子：
0
作者：
Lewis, Brittany B;Miller, Lauren E;Herbst, Wendy A;Saha, Margaret S
通讯作者：
Saha, Margaret S

Transcriptional dynamics during Rhodococcus erythropolis infection with phage WC1.

噬菌体 WC1 红平红球菌感染期间的转录动力学。

DOI：
发表时间：
2024-04-01
期刊：
影响因子：
4.2
作者：
Willner, Dana L;Paudel, Sudip;Halleran, Andrew D;Solini, Grace E;Gray, Veronica;Saha, Margaret S
通讯作者：
Saha, Margaret S