Researchers from Lund University have discovered the importance of the gene Cdc42 in tube formation and function in the pancreas. A team - led by stem cell and diabetes researcher Henrik Semb - studied two questions; how tubes are formed in organs where they fulfil vital functions and how cell differentiation is related to tube formation.  

Semb told Laboratory News: “Many epithelial organs like the lung, kidney, pancreas and salivary glands are primarily made of tubes. Understanding how cells polarise and coordinate tubulogenesis during organ formation is a central question in biology. Another important question is how tube formation regulates cell fate specification during organogenesis.”

Researchers characterised how tube formation occurs during pancreas organogenesis in mice and can explain step-by-step how cells in the pancreas form tiny cavities which eventually join together to create a system of tubes.  They can also explain how cells in different parts of the tube system become exposed to different environments and develop in different ways – some to produce insulin, others to produce enzymes to digest food, and others who help construct the tube itself.

The researchers - whose paper was published in Cell – removed Cdc42 from mice and discovered that no tubes formed in the pancreas.  This meant no insulin-producing beta cells were formed and the pancreas only generated enzyme-producing cells.

Semb said the study provides understanding of how cells polarise and establish tubular network during pancreas formation and that this can be used to understand other tubular organ systems.  “There is a great interest to develop insulin producing beta cells for cell replacement therapies in diabetic patients,” he told Laboratory News.

“Currently various differentiation protocols are developed to generate these cells from various stem/progenitor cells. Our results describing the importance of microenvironments can be incorporated to improve these differentiation protocols.”