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Extracellular regulation of Xenopus development

非洲爪蟾发育的细胞外调节

基本信息

批准号：
10237948
负责人：
Sergei Sokol
金额：
$ 41.7万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10237948
关键词：
Address Amphibia Animals Binding Biochemical Biological Cell Communication Cells Development Developmental Biology Developmental Process Disease Dorsal Ectoderm Cell Embryo Embryonic Development Event Fibroblast Growth Factor Gene Targeting Generations Genes Germ Layers Goals Growth Factor Health Human In Vitro Knowledge Ligands Location Malignant Neoplasms Mesoderm Molecular Molecular Analysis Mus Neuroectoderm Nodal Outcome Pathway interactions Pattern Pharmacotherapy Phosphorylation Play Post-Translational Protein Processing Proteins Regulation Role Signal Pathway Signal Transduction Signaling Molecule Spemann&apos s Organizer Structure TCF3 gene Testing Time Tissue Engineering Tissues Transcript WNT Signaling Pathway Wnt proteins Xenopus base beta catenin cellular targeting design differential expression embryo stage 2 embryo tissue experimental study extracellular gastrulation human disease human pluripotent stem cell in vivo loss of function molecular marker neural patterning neural plate novel novel therapeutics overexpression receptor transcriptome transcriptome sequencing vertebrate embryos xenopus development

项目摘要

Project Summary Vertebrate embryo body plan is established through cell-cell interactions driven by a small number of signaling pathways. The knowledge of these embryo-derived molecules and pathways has been instrumental for in vitro differentiation of mouse and human pluripotent stem cells and serves as a basis for tissue engineering. In amphibians, signaling from Wnt, BMP, FGF and Nodal-related ligands results in the formation of the Spemann organizer and subsequent tissue patterning. Many other extracellular factors regulate the time, location and level of these signaling events, and their discovery and analysis remain an important goal of basic developmental biology. This application focuses on the analysis of pinhead (pnhd), a conserved gene that we identified in a screen for Wnt target genes. Overexpression and depletion experiments suggest roles of pnhd in axial patterning, but its mechanism of action is currently unknown. Other preliminary studies show that Pnhd is a secreted protein that modulates Wnt- and BMP-dependent signaling in a region-specific manner. Based on this evidence, Pnhd is hypothesized to function as a new context- specific modulator of embryonic pathways. The proposed experiments will test this hypothesis by characterizing the developmental roles and functional effectors of Pnhd that are relevant to vertebrate axis specification and anteroposterior patterning. Other studies will address the molecular basis of the context-dependent effects of Pnhd on Wnt signaling. The mechanism of Pnhd action will be investigated using Xenopus embryos, in which biochemical and cell biological approaches can be combined with rapid functional analysis in the context of an intact animal. These studies will contribute to further understanding of signaling networks leading to body plan specification and patterning during early development. Since Wnt and BMP pathways have been implicated in many human cancers, the proposed experiments will unravel novel molecular mechanisms that operate during normal embryonic development and become frequently disrupted in disease.

项目总结