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Identification of the novel regulators for asymmetric cell division using genome wide RNAi screen

Objective

Asymmetric cell division, in which a cell divides into two cells of different developmental fate, is a fundamental mechanism for generating cell diversity. Although the significance of asymmetric cell division for development of multicellular organisms is widely recognized, asymmetric nature of stem cell division particularly attracts a great deal of attention because stem cells are sources of diverse cells in multicellular organisms and are valuable in regenerative medicine. Therefore, elucidation of the molecular mechanism governing asymmetric cell division will lead to not only comprehension of mechanism by which multicellular organisms are constructed but also improvement of therapy with stem cells.

To divide asymmetrically, cells must establish an axis of polarity to localize cell fate determinants to one side of the cells. During cytokinesis, these determinants are then segregated into one of the two daughter cells to give specific characteristics to only one cell. In the peripheral nervous system, sensory organ precursor (SOP) cells give rise to the four cells, two outer cells (hairs and sockets) and two inner cells (neurons and sheaths), to make up the external sensory (ES) organs through a series of asymmetric cell division. Several such cell fate determinants have been identified from Drosophila mutants with morphological defects of ES organs and the molecular machinery responsible for their asymmetric segregation is beginning to be unraveled in SOP cell lineage.

This project will take a novel systematic approach, genome wide RNA interference (RNAi) screen, to identify many other participants in the process of asymmetric cell division using Drosophila SOP cells. After the identification of the novel molecules responsible for asymmetric cell division through the screen, we plan to characterize the novel participants in fly SOP cells in detail, and then analyze the function of the vertebrate orthologue using mice lacking the molecules.

Call for proposal

FP6-2004-MOBILITY-7
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Coordinator

INSTITUTE OF MOLECULAR BIOTECHNOLOGY OF THE AUSTRIAN ACADEMY OF SCIENCES
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Dr. Bohrgasse 3-5
VIENNA
Austria

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