Press Releases 2006
Small regulators of key stem cell feature
Prof. Dr. Magdalena Götz, GSF- Institute of Stem Cell Research and Ludwig Maximilians University. [high resolution image, 300 dpi]
Dr. Timm Schroeder, GSF- Institute of Stem Cell Research. [high resolution image, 300 dpi]
Photos: Ulla Baumgart.
Neuherberg/München, 30 Oktober, GSF - National Research Center for Environment and Health (GSF). A key feature of stem cells is their capacity to self-renew as otherwise stem cells deplete during the generation of more differentiated progeny. The property that a stem cell can self-renew and generate itself as well as more differentiated precursors during cell division starts already in the developing embryo. For example, neural stem cells generate itself and precursors for neurons. A differentiated neuron is permanently postmitotic and can no longer divide. If the stem cells lack their self-renewing capacity, each division generates neuronal precursors only that then generate neurons and development ends at this point.
The factors that govern self-renewal of stem cells are not yet known. Recent work of the group of Magdalena Götz at the Institute of Stem Cell Research, GSF, and the Department of Physiological Genomics, LMU, has demonstrated that the small GTPase cdc42 is crucial for self-renewal of neural stem cells during development. GTPases are small molecular switches that activate other proteins when they are coupled to GTP, while they no longer activate these proteins when GTP is exchanged to GDP. The work by the Götz group in collaboration with the Schroeder group at the Institute of Stem Cell Research (Cappello et al., 2006) recently published in the September issue of Nature Neuroscience identifies the GTPase cdc42 as the molecular switch allowing self-renewal of neurl stem cells in the developing forebrain. They show that cdc42 is enriched at one end of neural stem cells and allows these to couple to each other. At the contact points between the stem cells crucial signalling components are then activated that allow the cells to divide asymmetrically, generating itself as well as another daughter cell specialized to generate neurons. If cdc42 is genetically deleted, neural stem cells loose their coupling and can no longer self-renew. This results in the premature generation of neuronal precursors and neurons and the eventual depletion of neural stem cells.
This work has broad implications for stem cell research. For examples, aging of stem cells has been linked to a reduced capacity to self-renew. Thus, activation of self-renewal of aging stem cells may allow to counteract the reduced capacity for repair in aging. Moreover, these finding prompt the idea to induce self-renewal capacity in other non-stem cells. Since the discovery of glial cells that were formerly regarded only as support cells in the nervous system, as the neural stem cells, this prompts the innovative approach to activate other glial cells to become stem cells. In the mammalian brain stem cells occur only in two small regions of the forebrain, including the human forebrain. Glial cells, however, are the most frequent cell type in the adult mammalian brain, even more numerous than neurons. Therefore the Götz group now aims to understand how ‘normal’ glial cells differ from those that act as neural stem cells and presently examines the role of cdc42 in glial cells of different adult brain regions.
Further information
- Paper: The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface. Nature Neuroscience 9 , 1099 - 1107 (01 Sep 2006) Article
- PubMed abstract: More...
- Download this release as pdf file: More...
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Neuherberg, 30 October 2006