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Molecular control of tissue morphogenesis

组织形态发生的分子控制

基本信息

批准号：
10214629
负责人：
Jennifer A Zallen
金额：
$ 33.72万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10214629
关键词：
1-Phosphatidylinositol 3-Kinase Adhesions Adhesives Bacteria Behavior Biochemical Biological Cell Communication Cell Culture Techniques Cell Polarity Cell Surface Proteins Cell Surface Receptors Cell membrane Cells Code Complex Cues Defect Development Developmental Biology Drosophila genus Embryo Family Family member Genetic Genetic Transcription Immune Response Genes Immune system Infection Innate Immune Response Innate Immune System Lead Leucine-Rich Repeat Ligands Link Lipids Location Maps Mediating Molecular Morphogenesis Movement Natural regeneration Nature Neoplasm Metastasis Output Parasites Pattern Phosphotransferases Physiological Process Property Proteins Receptor Activation Receptor Signaling Regenerative Medicine Regulation Role Shapes Signal Pathway Signal Transduction Structure Tissue Engineering Tissues Toll-like receptors Transcriptional Activation Translating Virus Work cell behavior cell motility convergent extension developmental disease experimental study extracellular fungus human disease imaging approach imaging modality in vivo insight novel pathogen quantitative imaging receptor receptor expression receptor function repaired response src-Family Kinases

项目摘要

A fundamental property of cells is their ability to act collectively to generate functional multicellular structures during tissue development, regeneration, and repair. An understanding of the mechanisms that organize cells into tissues is essential for treating developmental disorders and realizing the potential of tissue engineering and regenerative medicine. Cell- surface receptors expressed in precise patterns across tissues create spatial maps that control local interactions between cells and organize collective cell movements to establish tissue structure. How dynamic cell behaviors are organized in response to complex patterns of extracellular spatial information is not well understood. During convergent extension, the movements of hundreds of cells are systematically aligned with the tissue axes to elongate the body axis. This proposal aims to understand the mechanisms that regulate dynamic changes in cell polarity and interactions during this process, and to elucidate how cells respond to complex patterns of spatial information to achieve this conserved tissue structure. We discovered that three cell-surface proteins in the Toll receptor family create a spatial map that guides cell movements during convergent extension in Drosophila and directs the localization and activity of cellular proteins that generate contractile and adhesive forces within cells. Vertebrate Toll-like receptors respond to an extraordinary range of signals presented by fungi, bacteria, viruses, and parasites to elicit transcriptional changes that activate the innate immune response, but the mechanisms required for Toll receptor activation and signaling during convergent extension are not well understood. We will use genetic, cell biological, biochemical, and quantitative imaging approaches to determine how Toll receptors promote selective recognition between cells during development and identify the signaling mechanisms by which these receptors regulate cell polarity and behavior. Powerful genetic, cell biological, and quantitative imaging methods in Drosophila will be used to dissect the distinct spatial inputs of different members of this family of cell-surface receptors and investigate their functional contributions to cell behavior and tissue morphogenesis. These studies will elucidate mechanisms of Toll receptor activation and signaling and reveal general principles of tissue organization. A better understanding of how extracellular spatial cues are translated into changes in cell polarity and dynamics to establish tissue structure can provide insight into how the deregulation of these processes contributes to developmental disorders and human disease.

细胞的一个基本特性是它们集体行动以产生功能性细胞的能力。组织发育、再生和修复过程中的多细胞结构。的理解将细胞组织成组织的机制对于治疗发育疾病和实现组织工程和再生医学的潜力。储存格- 在组织中以精确模式表达的表面受体创建了空间图，细胞之间的局部相互作用，并组织集体细胞运动，结构动态细胞行为是如何组织的，以响应复杂的细胞外空间信息还没有被很好地理解。在收敛扩展期间，数百个细胞的运动与组织轴系统地对齐，体轴该建议旨在了解调节动态变化的机制，细胞极性和相互作用在这一过程中，并阐明细胞如何响应复杂的空间信息的模式来实现这种保守的组织结构。我们发现 Toll受体家族中的三种细胞表面蛋白创建了一个空间图，在果蝇的会聚伸展运动，并指导定位和活动在细胞内产生收缩力和粘附力的细胞蛋白质。脊椎动物Toll样受体对真菌，细菌，病毒，和寄生虫引发转录变化，激活先天免疫反应，但会聚延伸期间Toll受体激活和信号传导所需的机制是没有被很好地理解。我们将使用遗传、细胞生物学、生化和定量成像确定Toll受体如何促进细胞间选择性识别的方法发展和识别这些受体调节细胞的信号传导机制极性和行为。强大的遗传学、细胞生物学和定量成像方法，果蝇将被用来解剖这个家族的不同成员的不同空间输入，细胞表面受体，并研究其对细胞行为和组织的功能贡献形态发生这些研究将阐明Toll受体激活的机制，并揭示组织组织结构的一般原理。更好地了解如何细胞外空间线索被转化为细胞极性和动力学的变化，组织结构可以提供对这些过程的失调如何有助于发育障碍和人类疾病。

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Square Cell Packing in the Drosophila Embryo through Spatiotemporally Regulated EGF Receptor Signaling.

通过时空调节 EGF 受体信号传导在果蝇胚胎中形成方形细胞。

DOI：
10.1016/j.devcel.2015.09.015
发表时间：
2015
期刊：
Developmental cell
影响因子：
11.8
作者：
Tamada,Masako;Zallen,JenniferA
通讯作者：
Zallen,JenniferA

Myosin II dynamics are regulated by tension in intercalating cells.

DOI：
10.1016/j.devcel.2009.09.003
发表时间：
2009-11
期刊：
Developmental cell
影响因子：
11.8
作者：
Fernandez-Gonzalez R;Simoes Sde M;Röper JC;Eaton S;Zallen JA
通讯作者：
Zallen JA

Rho-kinase directs Bazooka/Par-3 planar polarity during Drosophila axis elongation.

Rho-kinase在果蝇轴伸长期间指导火箭筒/PAR-3平面极性。

DOI：
10.1016/j.devcel.2010.08.011
发表时间：
2010-09-14
期刊：
DEVELOPMENTAL CELL
影响因子：
11.8
作者：
Simoes, Sergio de Matos;Blankenship, J. Todd;Weitz, Ori;Farrell, Dene L.;Tamada, Masako;Fernandez-Gonzalez, Rodrigo;Zallen, Jennifer A.
通讯作者：
Zallen, Jennifer A.

Cellular, molecular, and biophysical control of epithelial cell intercalation.