Identification of Wnt Target Genes in the Neural Crest

神经嵴中 Wnt 靶基因的鉴定

• 批准号: 6880058
• 负责人: LISA T ZIEMER
• 金额: $ 5.05万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6880058
• 关键词: animal genetic material tag; biological signal transduction; cadherins; chick embryo; complementary DNA; cycloheximide; developmental genetics; ectoderm; functional /structural genomics; gene dosage; gene expression; gene targeting; in situ hybridization; neural crest; neural plate /tube; neurogenetics; nucleic acid quantitation /detection; polymerase chain reaction; postdoctoral investigator; protein tyrosine kinase; regulatory gene; vertebrate embryology

DESCRIPTION (provided by applicant): The neural crest is a migratory population of cells in vertebrate embryos that is induced at the boundary between the neural plate and non-neural ectoderm. While many studies have focused on the mechanisms underlying neural crest migration and differentiation, its origins from the ectoderm are less well understood. Recent experiments in our lab suggest that a Wnt signal appears to mediate this induction, but its molecular mechanism is not understood. Therefore, candidate genes expressed in the dorsal neural tube will be assessed for their dose and temporal responsiveness to Wnt signaling using a quantitative PCR assay. These putative targets will then be further analyzed for their regulation by B-catenin. To identify additional (and perhaps novel) genes involved in crest induction that are regulated by Wnt signaling, a genomics approach will be employed. To this end, chick homologs to genes identified in my graduate work to be Wnt responsive will be examined for their role in crest induction. In addition, cDNA macroarrays will be hybridized with cDNA isolated from neural plates cultured with Wnt conditioned medium. Thus, the long-term objective is to describe Wnt induction of the neural crest at a molecular level, and, in doing so, garner more knowledge concerning the development of various human craniofacial disorders and neural crest-derived cancers

描述（由申请人提供）：神经rest是脊椎动物胚胎中细胞的迁移群，在神经板和非神经外胚层之间的边界处诱导。尽管许多研究都集中在神经rest迁移和分化的基础机制上，但其起源于外胚层较少了解。我们实验室中的最新实验表明，Wnt信号似乎介导了这种诱导，但尚不清楚其分子机制。因此，使用定量PCR测定法，将评估在背神经管中表达的候选基因对Wnt信号的剂量和时间响应。然后，这些推定的靶标将通过B-catenin进一步分析其调节。为了鉴定由Wnt信号调节的额外（也许是新颖的）基因（也许是新颖的）基因，将采用基因组学方法。为此，将检查与我的研究生工作中确定的基因的雏鸡同源物，以应对响应性，以检查其在波峰诱导中的作用。另外，将与从Wnt条件培养基培养的神经板中分离的cDNA杂交cDNA宏观阵列。因此，长期目标是描述在分子层面上诱导神经rest的诱导，并在此过程中获得更多有关各种人类颅面疾病和神经rest衍生的癌症的知识的知识。