Award details

Control of stem cell proliferation in the arabidopsis root

Reference	BB/E022383/1
Principal Investigator / Supervisor	Professor James Murray
Co-Investigators / Co-Supervisors	Dr Walter Dewitte
Institution	University of Cambridge
Department	Institute of Biotechnology
Funding type	Research
Value (£)	418,060
Status	Completed
Type	Research Grant
Start date	01/07/2007
End date	31/12/2008
Duration	18 months

Abstract

The maintenance of stem cells during development is crucial in all multicellular organisms. A defining property of stem cells is the necessity for stringent controls on their proliferation, and the ability to reenter the cell cycle often in response to specific extrinsic factors or signals. Although a number of genes and functions that define specific stem cell identity have been identified, there is little understanding how these connect with and control the cell cycle. The root apical meristem (RAM) contains stem cells or initials that are progenitors of different cell lineages within the root. Recent evidence from the laboratory of Scheres shows that regulation of the retinoblastoma (RBR) pathway controlling progression through G1 and into S phase has a key role in stem cell maintenance in the Arabidopsis root. Reducing the level of RBR increases stem cell number, and conversely increasing RBR dissipates stem cells. However it is unclear how specific regulation of individual stem cell populations in the root is achieved, because RBR expression is not spatially localized. RBR activity is determined by phosphorylation by cyclin D (CYCD)-dependent kinases, in which CYCD forms the regulatory component. The applicant's lab has found recently that expression patterns of the ten Arabidopsis CYCD genes show striking cell type specificity in the root, with particular stem cell populations expressing different CYCD genes. In addition, he has isolated mutants in all CYCD genes, which show specific rate-limiting phenotypes in the predicted cell types. This proposal aims to test the hypothesis that CYCD expression is rate-limiting for stem cell maintenance in the Arabidopsis root, and that the specificity of expression determines the behaviour of different stem cell types. It will also establish whether CYCD genes are regulated by known determinants of stem cell identity, and whether there are functional differences between CYCD genes by promoter swaps in cycd mutants.

Summary

Stem cells are progenitor cells from which many other cells can arise, and are central to the development of all multicellular organisms because they provide a self-maintaining reservoir of unspecialized (or undifferentiated) cells that supply the precursor cells for tissue and organ formation. The maintenance of stem cells is therefore crucial for all multicellular organisms and is of outstanding significance for regenerative biology in medicine and agriculture. Given the life-long importance of stem cells, they are tucked safely from harm's way, in so-called stem cell niches that provide a microenvironment promoting self-renewal of the cells and inhibiting cell differentiation. Cell differentiation is associated with a cell ceasing to be a stem cell, acquiring the identity of a specialised cell type and stopping cell division. Plant stem cell niches are located in meristems at root and shoot tips, and are pivotal to the production of new organs and tissues throughout the plant life cycle that in some species can span several thousand years. Meristems are also major sites of cell division in plants, and are ultimately responsible for most of the growth of plants as well as the plastic modulation of growth in response to environmental signals and stress. In the Arabidopsis root meristem, stem cells for all the different root cell types surround a small group of organizing cells called the quiescent center, and together they form a stem cell niche. Although we know a number of genes that are required for stem cell function and which define stem cell identity, we have very little understanding of how the division of stem cells is controlled. The retinoblastoma-related (RBR) protein is found in animals and plants, and in mammals its loss is associated with cancerous cell proliferation. Recently it has been shown that RBR controls stem cell division in the root meristem of plants (Wildwater et al., 2005 'The RETINOBLASTOMA-RELATED Gene Regulates Stem Cell Maintenance in Arabidopsis Roots' Cell 123: 1337/1349). Loss of RBR increases stem cell number whereas increasing RBR levels results in their differentiation and loss of stem cell identity. However, we do not know how RBR is regulated differently to control division of the different types of stem cell in the root, because it is present in all of the cells. One factor known to control RBR activity is a group of proteins known as D-type cyclins (CYCD). In humans there are only three of these, but plants have much larger numbers of different CYCDs- ten in the model weed plant Arabidopsis. In work still unpublished, we have discovered that different stem cell types in the root express different CYCD genes, providing an explanation of how independent control of their proliferation can be achieved. We also find that in mutants lacking individual CYCD genes the proliferation of specific root stem cells is compromised. In this proposal, we build on these initial results and will test the hypothesis that proliferation of different stem cell populations depends on specific CYCD genes acting through the RBR pathway. We will also carry out experiments to address how the CYCD genes are regulated, and test whether all CYCD genes have equivalent functions. As a result, we will understand how stem cell division is regulated in the plant root, which is likely to have general implications for stem cells in other positions and other types of organism.

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	Plant Science
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

Associated awards:

BB/E022383/2 Control of stem cell proliferation in the arabidopsis root

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