Developmental Tuning of Turing Patterning

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Our bodies arrange their own parts appropriately before we are born. We have only one of certain body parts (e.g. head, nose, spleen) and two of others (e.g. arm, eye, big toe) of, and these achieve their position through an equivalent of an embryo's Global Positioning System. However, still other structures, like hairs or nephrons of the kidney, are very numerous - too numerous to have a dedicated placing of each and every one of them. Instead, the body seems to use a simple "rule" to lay out these structures. This "rule" involves local interactions between cells which make sure that each follicle, nephron, or other structure, forms at a set distance from others of the same kind. Theoretical biologists have provided and proven general concepts that could underlie the operation of these "rules" and recent work by molecular biologists has substantiated and extended these theoretical ideas, identifying the specific genes and proteins that act as to set the "rule".However, structures like hair follicles are not homogeneous across the body. For example, the eyebrows and scalp produce thicker hair types that mark these parts of the skin as being different from, for example, the forehead, which has very small, fine hairs. In this proposal we aim to understand how such distinctions in pattern, in this case of hair follicles serving as an example of other repeated structures, can be achieved. In essence, we will go up one level in organisation to understand how the size and spacing "rule" can be varied in different locations. This we will do by studying hair follicle formation on different parts of the mouse skin, with a focus on the various whiskers because of their distinctive pattern. Our project will be a combination of molecular and cell biology in analysing and manipulating the signals that pass between cells and mathematical simulations to interpret and guide the experimentation. Experiments will be done primarily on cultured skin samples, sparing use of intact animals. The intended outcome is to understand at both molecular and conceptual levels how the body can utilise a single pattern forming system by tuning in different regions to achieve a complex anatomy.