How does a single cell type build diverse shapes and structures during skeletal development?

Skeletons are widespread across animals on planet earth. Within our skeletons, but also the skeletons of most animals, there are hundreds of differently-shaped and -sized elements. A femur, for instance, is distinct from a pelvis and a skull. In vertebrates, skeletons are made out of bones, but other animals across the tree of life have different, but equally vital hard, crystalline structures providing support and protection. These skeletal structures, as well as human bones, are called biominerals, because they are produced by biological processes. Biomineralised skeletons are built by the activity of specialised cells which exhibit precise control over the size, shape, and orientation of the crystals they build. How these cells can produce hundreds of different skeletal elements with diverse shapes and sizes, all within a single organism, remains unclear. Animal growth and development relies on signalling pathways, a group of molecules which help cells to send and receive information from their surrounding environment. We aim to test the hypothesis that the different activity of signalling molecules around skeletal cells regulates the shape, size, and ultimately the diversity and complexity of skeletal elements during development. Understanding how biomineralising cells build different skeletal elements is crucially important, as these processes occur as a part of normal development in every human, and billions of other animals on planet earth. The World Health Organisation lists musculoskeletal conditions as the leading cause of disability worldwide, effecting 1.71 billion people. Specifically, skeletal dysplasias, where bones form abnormally, can result from dysregulation of signalling pathways during development. Thus, while our proposed work is basic science, it has the potential to inform on fundamental biological mechanisms relevant to human health. During skeletal development, a low number of cell types is able to construct highly complex and diverse tissues. An extreme case of this phenomenon is exemplified by the sea urchin, our model system for the proposed research. The sea urchin skeleton includes hundreds of differently-shaped skeletal elements, all of which are built by a single type of cell, called the sclerocytes. This makes the sea urchin an ideal model species in which to understand how signalling pathways interact with a single cell type to build a vast array of skeletal shapes and sizes. We will address three primary hypotheses with our proposed work: (1) differential signalling regulates sclerocyte position in specific skeletal elements; (2) signalling mediates differences in gene expression in sclerocytes across the skeleton; and (3) variation in shape, size, and complexity of elements is the result of different signalling pathways. We will test our first two hypotheses by analysing developmental gene expression during development in high resolution, and experiments on signalling pathway function. To test the third, we will use micro-CT scanning and harness artificial intelligence by using deep learning-assisted image processing to produce and analyse a massive dataset of skeletal anatomy. All together, our approach will span from genes and cells, up to biomineralised anatomy, providing a holistic, whole-organism understanding of development. Specifically, our work will answer a crucial question at the heart of skeletal biology: how do molecular and cellular processes shape different parts of the skeleton. In doing so, we will produce novel comparative resources for skeletal and developmental biologists and clarify the general mechanisms of how skeletons grow and develop across the tree of life.