Grant: Discovery Grants Program - Individual

Endoderm is a term that describes the interior layer of an early embryo. This layer will generate a simple tubethat will give rise to many important organs including the thyroid, lung, pancreas, liver, and stomach. Theseorgans arise from specific points along the tube in a precise spatial order. The thyroid comes from the veryfront of the tube and the lung comes from endoderm located further back. At the earliest stages ofdevelopment, these two regions share many genes that are essential for their eventual development and so wewish to discover what makes the two organs different. We have found that addition of retinoic acid, the activeform of vitamin A, causes the thyroid to turn off several important thyroid genes and turn on genes that arenormally only expressed in lung. Our goal is to understand this switch in developmental fate. We will alsoexploit this switch to search for new genes that important for making a thyroid or a lung. Once we haveobtained genes that are expressed in one organ or the other, we will manipulate those genes to examine theireffect on thyroid and lung differentiation. By doing so we hope to gain a better understanding of the molecularnetwork needed for the normal development of these endodermal organs.