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One of our long-term goals is to elucidate the molecular program controlling liver development. The liver provides many essential functions, and numerous liver pathologies are so life-threatening that transplantation is the only option.
Despite its physiological importance, the molecular basis of liver development is poorly understood. A better understanding will provide insight into congenital liver disease and facilitate efforts to produce therapeutically useful hepatic tissue from stem cells.
Over the last 10 years, studies have shown that FGF and BMP growth factors secreted from the heart mesoderm induce the liver from a subset of the foregut endoderm tissue. As a result the undifferentiated liver precursor cells known as “hepatoblasts” delaminate from the foregut epithelium and invade the adjacent mesenchyme to form the growing liver bud – a bulb of tissue emerging from the primitive gut tube. However, there are a number of important steps in this process that are not well understood and which our research is attempting to address using frog and mouse embryos as experimental models.
Learn more about liver development.
The results of this proposal will provide novel information on the molecular mechanisms governing early hepatic development.
McLin VA, Rankin SA, Zorn AM. Repression of Wnt/beta-catenin signaling in the anterior endoderm is essential for liver and pancreas development. Development. 134:2207-2217. 2007.
Zorn AM, Mason J. Gene expression in the embryonic Xenopus liver.Mech Dev. 103:153-157. 2001.
click to enlarge
(A) A transgenic mouse embryo (foxa3cre;Rosa26R) at 9.5 days of development stained for β-galactosidase expression in the gut epithelium and liver diverticulum (l.d.), from which the liver bud grows. (B) A transverse section through the liver bud of the embryo in (A) stained with anti-HNF4α antibodies, shows the endoderm in blue and the HNF4α-expressing hepatoblasts invading the mesenchyme.
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