The Lineage of the Midgut Definitive Endoderm

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The early embryo is composed of three types of tissues; the ectoderm will form the brain, nervous system and skin; the mesoderm will form bones, muscles, and organs such as heart, kidneys, ovaries and testis; and endoderm or gut will form tissues of the respiratory and gastrointestinal tract including organs such as lungs, liver, pancreas, intestine and colon. My laboratory is focused on understanding how endoderm develops into the diverse array of organs that comprise the respiratory and gastrointestinal tracts. The endoderm forms a sheet of cells that cover the belly side of the embryo. Through cell-to-cell communication, cells are instructed to form the different organs of the gut in the correct order along the gut tube so that they function normally. Our proposal focuses on the expression and functions of a gene called Nephrocan (Nepn). We have shown that Nepn is exclusively expressed in the midgut region of the embryo that is thought to form the intestine and part of the pancreas. Experiments in the lab have shown that Nepn inhibits a communication pathway known as TGF? suggesting that inhibition of this pathway is required for midgut formation. In our project, we will use the Nepn gene to trace the cells of the midgut to determine their organ fate. We will also examine how the expression of Nepn is restricted to the midgut. Finally, we will determine the functions of Nepn by deleting the gene in the mouse. Together, these experiments will allow us to understand how the midgut forms and the role of Nepn in midgut formation.