Pancreas Development

Researchers have discovered a key clue into the development of the pancreas and brain by studying rare patients born without a pancreas. The study from the Wellcome Sanger Institute, the University of Exeter and collaborators also identify a previously unexpect pathway involve in the development of the human pancreas, and confirm.
Publish today (18th April) in the American Journal of Human Genetics; so the study revealed that all three patients without a pancreas; also with abnormal brain development had an identical change in the CNOT1 gene. The team went on to show how this genetic change kept stem cells in their original state; so preventing them from developing into pancreatic cells.

Insulin making cells in pancreas

Type 1 diabetes develops when insulin-making cells in the pancreas, called beta cells; hence are attack by the immune system. People with this disease need daily injections of insulin to control their blood sugar levels. Replacing the damage pancreatic cells with cells derive from stem cells could treat the disease; but the pancreatic development pathways are not yet fully know.

To learn more about the development of the pancreas; hence researchers from the University of Exeter studied the genetics of 107 international patients with pancreatic agenesis. They discover that three unrelated patients with very similar clinical features; including a possible neurological disorder; so had an identical mutation in the CNOT1 gene. This gene had never implicate in pancreatic or brain development before.

The Wellcome Sanger Institute researchers then bred mice with this mutation in the mouse version; so the gene to see how it affect development. They find the mouse embryos with the mutation in Cnot1 had a much smaller upper pancreas than usual; so directly linking the Cnot1 gene with pancreas development. They also saw changes in the mouse brain development.
Dr Elisa De Franco, co-first author from the University of Exeter Medical School, said: They find that three patients with pancreatic agenesis had an identical spelling mistake in the CNOT1 gene. This was the first time that anyone had realize that CNOT1 was important in pancreatic and neurological development; also has reveal a new genetic cause for pancreatic agenesis.

Collaboration between clinical

Through a great collaboration between clinical and mouse research disciplines; hence they have provide compelling evidence that the CNOT1 gene is involve in the formation of the pancreas in both humans and mice. We are now able to investigate the developmental mechanism; so to understand how the pancreas develops.
The CNOT1 gene had previously been implicate in keeping human and mice embryonic stem cells in a state where they can develop into any type of cell, know as pluripotency. Studying which genes were active in the developing mouse pancreas; so the researchers discover that the Cnot1 mutation change the levels of a key developmental factor, preventing the stem cells from developing.
Dr Rachel Watson, a joint first author from the Welcome Sanger Institute, said: “Once we knew the CNOT1 gene was involve in pancreatic development, they want to find out how it worked. Changes in some developmental factors in Cnot1 mutant mice indicate that the stem cells remain as stem cells, rather than developing into pancreatic cells. This suggest an entirely new mechanism for pancreatic agenesis, which involve maintaining stem cells in a pluripotent state.