DICTYOSTELIUM
Many biological processes important to the development and health of humans are dependent on controlled cell movement. These processes include, 1) metastasis of cancer cells (movement of cells to another part of the body); 2) chemotaxis of cells of the immune system (directed movement of cells in relation to chemical agents)3) movement of primordial germ cells that give rise to both sperm and eggs; 4) migration of the neural crest, which is the precursor of the peripheral nerves, pigment cells, and valves of the heart; 5) gastrulation (process of making the three germ cells required for developing an embryo); and 6) cell sorting during embryonic pattern formation. Examining the regulation of these processes at the molecular level is important to our understanding of genetically inherited diseases associated with failures in cell migration. In the case of cancer, this information can lead to the effective design of chemotherapeutic agents. Genetically accessible systems can be used to identify new regulatory pathways involved in cell migration.
One organism that has been the subject of intense studies is Dictyostelium. Dictyostelium is a single cell amoeba that will organize into a multicellular organism under the appropriate environmental conditions. The cells aggregate into mounds that are fated to form either a stalk or a spore. This aggregate transforms into a migrating slug (pseudoplasmodium) that moves in response to changes in temperature and light. When the slug finds the appropriate environmental conditions, the slug transforms into a fruiting body with a stalk and spores. The spores will give rise to a new generation of single celled amoebae.
Transgenic Dictyostelium expressing green fluorescent protein (GFP) have been created by Dr. Rick Firtel (University of California, San Diego) for the purpose of following the movement of individual cells within the forming slug and fruiting body. Because GFP can be visualized in living cells, researchers are able follow cell movement without interrupting the development of the aggregate. The GFP Dictyostelium have been specifically been used to assess the potential role of calcium in regulating cell sorting and morphology as well as the regulation of prestalk- and prespore-specific gene expression.
R.A. Firtel and R. Meili. Dictyostelium: a model for regulated cell movement during morphogenesis. Current Opinion in Genetics & Development 10, 421-427 (2000)
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A.B. Cubitt, I. Reddy, S. Lee, J.G. McNally, and R.A. Firtel. Coexpression of a constitutively active plasma membrane calcium pump with GFP identifies roles for intracellular calcium in controlling cell sorting during morphogenesis in Dictyostelium. Developmental Biology 196, 77-94 (1998).
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