Role of the Polycomb group gene Cbx4 in the control of skin regeneration and wound healing

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The skin is an organ that covers the body and protects us from a variety of environmental insults, such as mechanical injury, invasion of microorganisms, ultra-violet irradiation and also prevents water loss. To fulfil such important function, skin has to constantly regenerate itself throughout of a person's life, and this ability of the skin for self-regeneration relies on proper functioning of epithelial stem cells present in the epidermis and hair follicles, the major epithelial structures of the skin. These stem cells are long-living cells, while producing short-living specialised progenies that form all protective epidermal cell layers and hairs. As the skin ages, functional activities of the stem cells decline leading to a thinning of the epidermis and hair loss, as well as reducing their ability to regenerate the skin after injury. Data obtained during the last decade have revealed that there are multiple cellular biochemical pathways controlling skin stem cells activity, with recent data demonstrating that activity of these biochemical pathways can be governed by epigenetic regulatory mechanisms. One of such epigenetic mechanisms is the modification of histones, proteins closely interacting with DNA, by the Polycomb group proteins to repress the expression of genes and thus change many important cellular functions.This project will look at how a Polycomb group gene Cbx4, which represses many genes, impacts on normal physiological and injury-induced regeneration. We will also explore how Cbx4 regulates different molecular signals in the epithelial stem cells and their progenies (those which form the epidermis and hair), and their involvement in wound healing. In addition, we will examine how Cbx4 controls long-term survival of the skin stem cells and their ability to produce skin-specific progeny.Studying the skin as a model system in this way, will cast light on the mechanisms that control the development and regeneration of other epithelial tissues, such as the epithelia of the intestine, teeth, kidney and lung. The knowledge gained from this study will therefore provide new opportunities to aid in the development of novel epigenetic therapies intended to prevent aberrant tissue growth and regenerative limitations, such as impaired wound healing in diabetic patients and in elderly individuals.