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Control of epidermal self-renewing populations by bHLH and MAPK regulatory system

bHLH 和 MAPK 调节系统控制表皮自我更新群体

基本信息

批准号：
8895980
负责人：
DOMINIQUE C BERGMANN
金额：
$ 7.4万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8895980
关键词：
Arabidopsis Behavior Biochemical Biological Assay Blood Cancerous Cell Lineage Cell division Cells Chromatin Data Data Set Development Dimerization Disease Ensure Epithelium Gene Expression Gene Expression Profile Gene Family Genes Genetic Genetic Screening Goals Harvest Human In Vitro Injury Lead Location MAP Kinase Gene MAPK Signaling Pathway Pathway Maintenance Malignant Neoplasms Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinases Molecular Molecular Genetics Molecular Profiling Monitor Muscle Mutation Natural regeneration Organ Pathway interactions Phenotype Phosphorylation Population Process Proteins Regulation Signal Transduction Staging Stem cells System Testing Tissues Variant Work adult stem cell base chromatin immunoprecipitation design functional genomics gain of function gene function genomic tools in vivo induced pluripotent stem cell member novel prevent response self renewing cell self-renewal stem stem cell differentiation tissue repair transcription factor tumor

项目摘要

Summary Self renewal is integral to the creation and maintenance of many tissues and organs including human epithelia, muscle and blood systems. Each of these tissues establishes populations of self-renewing (stem) cells and must ensure that these stem cells divide and create new differentiated cells at the appropriate rate and in the appropriate place; not enough cells or divisions and the tissue will deteriorate, too many divisions and tumors can form. Our long term goal is to understand the mechanism(s) by which dispersed self-renewing populations are established and how their division and differentiation is influenced by interaction with neighboring cells. A powerful set of genetic, molecular and functional genomic tools, combined with the ability to visualize and track cell divisions makes Arabidopsis stomatal development an attractive system for investigating this set of questions. In our previous work we found that a trio of bHLH transcription factors and components of a MAPK pathway modulate division vs. differentiation choices at discrete stages in stomatal development. Based on data from genetic, biochemical and functional assays, we propose that activity of the earliest-acting bHLH in this trio, SPEECHLESS (SPCH), controls the asymmetric divisions that create the self-renewing populations. We show that SPCH is a direct target of MAP kinase-dependent phosphorylation in vitro, and that phosphorylation alters the behavior of SPCH in vivo. Our specific aims in this proposal are to: (1) elucidate the molecular mechanisms by which SPCH activity is regulated (2) Create a molecular profile of stomatal lineage cells and identify and functionally characterize transcriptional targets of SPCH in these cells, and (3) Take advantage of SPCH-induced phenotypes to genetically dissect the endogenous signaling network required to repress stem-cell differentiation. Because both the bHLH class of transcriptional regulators and the MAPK pathway are universally conserved, these studies may contribute not only to an understanding of self-renewal, but will contribute to our understanding of the diversity of MAPK and bHLH signaling mechanisms and responses.

总结

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）

The secret to life is being different: asymmetric divisions in plant development.

DOI：
10.1016/j.pbi.2010.09.016
发表时间：
2010-12
期刊：
Current opinion in plant biology
影响因子：
9.5
作者：
Tomasz Paciorek;D. Bergmann
通讯作者：
Tomasz Paciorek;D. Bergmann

Direct Control of SPEECHLESS by PIF4 in the High-Temperature Response of Stomatal Development.

DOI：
10.1016/j.cub.2018.02.054
发表时间：
2018-04-23
期刊：
Current biology : CB
影响因子：
0
作者：
Lau OS;Song Z;Zhou Z;Davies KA;Chang J;Yang X;Wang S;Lucyshyn D;Tay IHZ;Wigge PA;Bergmann DC
通讯作者：
Bergmann DC

Generation of spatial patterns through cell polarity switching.