Membrane and mechanical signals guiding islet morphogenesis

The islets in the pancreas are groups of hormone-secreting cells, including insulin-producing beta cells, which are critical for controlling blood sugar levels. Islets have a distinct three- dimensional structure which is required for beta cells to be fully active. The disease diabetes develops when beta cells are lost or dont function properly. To discover new ways to treat diabetes, it is important to understand how pancreatic islets form. In the pancreas, endocrine cells start off separated and move together to form the islets. The details of this clustering process is not well understood because the pancreas is located deep inside the body. The goal of the project Membrane and mechanical signals guiding pancreatic islet morphogenesis is to learn more about islet formation using the model organism zebrafish. Zebrafish are ideal for this research because their pancreas develops much like a humans, and they are small, easy to handle, and transparent at early stages, allowing scientists to watch cells move in real time. In this research project, we take advantage of live microscopy to understand the time sequence of islet formation. In our previous studies, we discovered that islet cells actively change shape and extend thin processes during islet formation. These protrusions are likely important for cell-cell recognition and making contacts between cells, and they help cells to actively pull towards each other as they assemble. We predict that proteins and other molecules at the cell surface are important for conducting mechanical forces and directing cell movements. We will use new high-resolution methods for looking at the activity of membrane factors and detecting tension. We will study the effect of blocking the function of membrane factors and mechanical transducers, in order to define their role in islet formation. We will also look at whether similar molecules may be playing the same role in islet development in mammals including humans. Insight gained from these studies can improve methods for producing replacement islets to treat diabetes. These same membrane factors play a role in the development of many organs such as the heart and nervous system, and in diseases such as cancer, so that our studies can help to understand other diseases and lead to new treatments.