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Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing, immune responses all require the orchestrated movement of cells in a particular direction to a specific location. Errors during this process have serious consequences, including mental retardation, vascular disease, rheumatoid arthritis, tumor formation and metastasis. Understanding the mechanisms through which cells migrate is therefore of great importance for the development of novel therapeutic strategies, tissue engineering, and our understanding of cellular transplantation.
Cell migration is a wide and multidisciplinary area of research which has captured the attention of many cell biologists, immunologists, neuroscientists and biophysicists. Recent technical advances, particularly in genetic engineering and microscopy, have greatly contributed to cell migration research.
In order to migrate, cells have to sense extracellular chemotactic molecules through specialized receptors on their cell membranes. Receptor activation triggers signalling cascades that lead to cell movement. Briefly, cells migrate by first extending a protrusion at the front or leading edge, towards the direction they will move in. Once the protrusion is stabilised, by adhering to the extracellular matrix, the rear of the cell releases its attachments to the substrate and contracts, aiding the forward flow of the cytosol and facilitating forward advance.
Changes in the cytoskeleton and cell adhesion underlie the changes in cell shape and motility, hence many studies have focused on the molecular mechanisms which regulate cytoskeletal dynamics and the turnover of adhesions. While the polymerisation of actin filaments has a well established role in driving the formation of protrusions, microtubules have also emerged as key players in cell migration. Microtubules facilitate cell migration by becoming selectively stabilised at the leading edge and by triggering the dissassembly of focal adhesions. The retraction of the rear of the cell also involves actomyosin-based contractility.
Since the molecular processes that take place at the front and rear of the cell are different, migrating cells are said to be polarized. The establishment and maintenance of cell polarity in response to extracellular signals has also been subject of intense investigation. Time-lapse studies in living cells have enabled the visualisation of distinct signalling domains at the front and back of migrating cells. While PIP3, active CDC42 and Rac are restricted to the front of the cell, Rho, PTEN and myosin II are typically found at the rear.
Cell migration is an exciting and rapidly evolving field as evidenced in the Cell Migration Gateway, a new online resource where one can freely access the latest findings in cell migration research, primary data generated by scientists from the Cell Migration Consortium, as well as factfiles for molecules relevant to cell migration. Many key regulatory molecules have been identified and conserved signalling pathways are emerging. However, many questions regarding how cells integrate multiple extracellular signals to reach their targets or establish the temporal and spatial segregation of signalling components will keep researchers busy for years to come.
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"Cell migration"