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The development of multicellular organisms involves a single cell (such as a fertilized egg) which gives rise to a diverse progeny through successive cell divisions. The process of cell division in which the resulting daughter cells are of different characters or “fates” is known as asymmetric cell division. One example of this form of cell division is seen in stem cells, which can produce one copy of themselves and one more specialized (differentiated) cell in a single division. Asymmetric cell division is central to the generation of cellular diversity, but because in higher organisms a given cell's “family relations” (known as cell lineage) are frequently unclear, it can be difficult to study the process in detail.
In the nematode, C. elegans, however, thanks to the transparency of the worm's body it is possible to track the division and other activity of individual cells in the living animal using only a low-magnification light microscope. In our laboratory, we take advantage of this ability to monitor developmental processes in real time, a method which we use in combination with genetic studies to investigate the mechanisms that underlie asymmetric division. We have determined that nearly every asymmetric cell division in C. elegans is mediated by β-catenins acting in the Wnt signaling pathway. This pathway works to polarize cells fated to undergo asymmetric division; we seek to gain a better understanding of how it achieves this by studying the intracellular localization of the Wnt pathway's molecular components.
We have also discovered numerous mutant C. elegans phenotypes in which the asymmetric division of specific cells is disturbed, allowing us to identify more than 50 genes involved in this process. By investigating the function of these genes, we hope to clarify the biological mechanisms of asymmetric cell division even further.