The role of Wnt proteins in symmetric/asymmetric division of the mammary stem cells

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Asymmetric division of a stem cell produces one stem cell and a differentiated cell. For example, a single mammary stem cell can self-renew and give rise to luminal or myoepithelial cell types of the mammary gland. Our understanding of extrinsic cues in this process is scant. Wnt proteins are key players in the establishment of cell polarity and work in stem cell self-renewal, including in the mammary gland. To understand the role of Wnt signals, I aim to reveal the Wnt expression profile in the mouse mammary stem cell (MaSC) niche by in situ hybridizations and antibody stainings. Next, I will study the direct effect of recombinant Wnt proteins on the division mode of purified MaSC. I propose a strategy that directs the Wnt proteins to only one side of the cell and therefore allows the induction of cell polarity. Furthermore, I will examine the effect of other signaling molecules on the mode of the cell division. Finally, by applying protein co-purification methods, I will investigate potential interactions between down stream components of the signaling pathways and the proteins involved in the establishment of the cell polarity. Overall, my proposed study will explore a general basic mechanism that other stem cells may also use.