Integration of tissue mechanics and cell signalling in developmental patterning of the skin

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The project aims to understand how tissue mechanical and cell signalling processes are integrated to produce repeating patterns of cell fates in embryonic development. The focus is on the skin, an organ with two constituents: a continuous sheet of cells called the epidermis covering a looser arrangement of cells called the dermis. This type of composite structure that involves a sheet of cells on top of a matrix containing scattered and motile cells is found in a wide range of organs, including the intestine, lung, kidney, and mammary and salivary glands. Such organs are almost invariably composed of an intricate pattern of small repeating structural elements. This proposal focuses on the repeated elements in the avian skin, the feather follicles, while in other organs the repetition can produce a branched tree, or fingerlike projections, to attain a greater surface area. There is emerging evidence that these and other structures are formed not only from cell signalling interactions and local cell movement, but also by poorly-characterised mechanical and physical inputs which are generated by and responded to by cells. Much of our knowledge on mechanical influences on cell behaviours comes from culture experiments performed on isolated cells, absent the context of a complex tissue environment. This project will use the rapidly developing chicken embryonic skin to define the physical differences in local tissue environment, identify how these physical differences arise and are regulated, and determine their effects on intercellular communication, fate determination and pattern formation.We will use chicken embryonic skin for the project due to its large size, ease of manipulation, the availability of suitable genetic lines for tracking and modulating developmental processes, and the early embryonic stage at which developmental events take place, avoiding use of animals in experimentation. From experiments done to date we know that cell motion, cell signalling, and tissue stretching/compression are together key to the production of feathers and their specific spacing arrangement. We will use recently generated lines of chicken allowing visualisation and manipulation of cells and engineering approaches to ask how these processes are integrated with the mechanical/physical changes that cooperate to drive embryonic pattern formation.