The overall goal of this proposal is to understand how cell polarity is generated and maintained during animal development. Our approach is to identify and study genes involved in the control of cell polarity by identifying mutations that disrupt the polarities of individual cells. Proper cell polarity requires both the generation of cellular asymmetry and the orientation of the asymmetric cell to the body axis. For example, mutations in the C. elegans Wnt gene Iin-44, primarily cause the polarities of certain cells in the tail to be reversed with respect to the body axis, whereas mutations in the frizzled-related gene lin-17, primarily cause those same cells to loose their polarity. To understand how cell polarity is controlled we must understand both the generation of asymmetry and its orientation to the body axis. In addition, the mechanisms by which cell signals influence cellular architecture to establish cell polarity are not clear. The proposed experiments will help elucidate the link between Wnt signaling and establishment of asymmetric cellular structure. New genes involved in cellular asymmetry and polarity we identify may be previously unknown and could be involved in coupling polarity signals to cell structure. We have shown that t/p-i function is required for cellular asymmetry. Furthermore, tip-I is asymmetrically expressed in the posterior daughter of an asymmetric cell division and responds to LIN-44/Wnt signaling.
We aim to differentiate mutants that affect the generation of cellular asymmetry and polarity from those that affect execution by their effect on tip-I asymmetric expression.
We aim to analyze two genes, tcl-1 and tcl-2, that appear to be involved the generation of cellular asymmetry. We also aim to analyze sli-2, mutations in which suppress the polarity reversals of lin-44 mutations, suggesting that sli-2 may function in the orientation of cell asymmetry, perhaps as a new component of the Wnt signaling pathway.
We aim to identify the elements within the tip-I promoter required for asymmetric expression as well as to identify trans-acting factors required for tip-I asymmetric expression by identification of mutations that disrupt tip-i asymmetric expression. By doing so, we can work our way backwards through the cell polarity pathway. Finally, we aim to determine whether a spatially localized LIN-44 signal is required for proper cell polarity
| Hajduskova, Martina; Jindra, Marek; Herman, Michael A et al. (2009) The nuclear receptor NHR-25 cooperates with the Wnt/beta-catenin asymmetry pathway to control differentiation of the T seam cell in C. elegans. J Cell Sci 122:3051-60 |
| Wu, Mingfu; Herman, Michael A (2007) Asymmetric localizations of LIN-17/Fz and MIG-5/Dsh are involved in the asymmetric B cell division in C. elegans. Dev Biol 303:650-62 |
