Abstract

The ability of stem cells to develop into a large variety of different cell types holds great promise for treatment of many human diseases. Furthermore, the control of the growth of stem cells and other unspecified cells is critical to prevent the development of cancer. Underlying these processes are fundamental aspects of cell biology involved in signaling between cells, and the control of cell orientation. This proposal seeks to address these issues by studying the fundamental regulation of stem cell specification, differentiation, and polarity as controlled by the CLV signaling pathway in Arabidopsis. The long-terms goals are to understand mechanism by which the delicate balance between stem cell proliferation and differentiation is maintained, and the mechanism by which CLV signaling regulates these processes. The CLV signaling pathway is a key factor -the loss of any component in this pathway leads to massive accumulation of stem cells at the expense of differentiation. Recent findings in the field have uncovered novel components of the signaling pathway, and provided key insights into the mechanism of CLV signaling. This proposal will explore the role of the POL/PLL1 phosphatases in signaling and the establishment of cell polarity. Receptor sub-cellular localization will be addressed, along with receptor co-localization and interaction with putative downstream effectors. Preliminary evidence of receptor association with lipid rafts will be rigorously tested. The role of cofilin, which binds to the CLV1 receptor-kinase, will tested through a combination of genetic, localization and protein interaction approaches. The structure/function and possible maturation of the putative ligand CLV3 will be investigated. A BY-2 cell culture system will be developed to integrate these different experimental lines in a way that addresses receptor activation and mechanism of signaling. The results of these experiments will provide major steps forward in understanding these key developmental processes. ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM062962-06
Application #
7190537
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Haynes, Susan R
Project Start
2002-02-01
Project End
2010-02-28
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
6
Fiscal Year
2007
Total Cost
$291,170
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Lee, Chunghee; Clark, Steven E (2015) A WUSCHEL-Independent Stem Cell Specification Pathway Is Repressed by PHB, PHV and CNA in Arabidopsis. PLoS One 10:e0126006
Gish, Lindsey A; Gagne, Jennifer M; Han, Linqu et al. (2013) WUSCHEL-responsive At5g65480 interacts with CLAVATA components in vitro and in transient expression. PLoS One 8:e66345
Guo, Yongfeng; Ni, Jun; Denver, Robert et al. (2011) Mechanisms of molecular mimicry of plant CLE peptide ligands by the parasitic nematode Globodera rostochiensis. Plant Physiol 157:476-84
Gish, Lindsey A; Clark, Steven E (2011) The RLK/Pelle family of kinases. Plant J 66:117-27
Gagne, Jennifer M; Clark, Steven E (2010) The Arabidopsis stem cell factor POLTERGEIST is membrane localized and phospholipid stimulated. Plant Cell 22:729-43
Guo, Yongfeng; Han, Linqu; Hymes, Matthew et al. (2010) CLAVATA2 forms a distinct CLE-binding receptor complex regulating Arabidopsis stem cell specification. Plant J 63:889-900
Gagne, Jennifer M; Gish, Lindsey A; Clark, Steven E (2010) The role of the acyl modification, palmitoylation, in Arabidopsis stem cell regulation. Plant Signal Behav 5:1048-51
Guo, Yongfeng; Clark, Steven E (2010) Membrane distributions of two ligand-binding receptor complexes in the CLAVATA pathway. Plant Signal Behav 5:1442-5
Song, Sang-Kee; Hofhuis, Hugo; Lee, Myeong Min et al. (2008) Key divisions in the early Arabidopsis embryo require POL and PLL1 phosphatases to establish the root stem cell organizer and vascular axis. Dev Cell 15:98-109
Deyoung, Brody J; Clark, Steven E (2008) BAM receptors regulate stem cell specification and organ development through complex interactions with CLAVATA signaling. Genetics 180:895-904

Showing the most recent 10 out of 19 publications