from SECTION I - PATHOPHYSIOLOGY OF PEDIATRIC LIVER DISEASE
Published online by Cambridge University Press: 18 December 2009
The liver is derived from the endoderm, one of the three germ layers formed during gastrulation. The initial endodermal epithelium consists of approximately 500 cells in the mouse [1], from which cells will be apportioned to the thyroid, lung, stomach, liver, pancreas, esophagus, and intestines. How is the endoderm patterned to generate such diverse tissues? Once the hepatic primordium is formed, how are the different hepatic cell types generated? How do they generate a proper liver architecture? And how do the principles of liver development apply to liver regeneration and the possibility of generating hepatocytes from stem cells? This chapter focuses on all of these questions.
A BRIEF OVERVIEW OF EMBRYONIC LIVER DEVELOPMENT
By late gastrulation in the mouse (embryonic day of gestation 7.5 [E7.5]) the anteroposterior pattern of the endoderm is already established [2], so that during E8.5–9.5 (mouse) the anterior-ventral domain develops the organ buds for the liver, lung, thyroid, and the ventral rudiment of the pancreas [3]. This corresponds to about 2–3 weeks' gestation in humans. The specification of liver progenitors occurs through a combination of positive inductive signals from the cardiogenic mesoderm and septum transversum mesenchyme and repressive signals from the trunk mesoderm [4–6]. This occurs at about 8.5 days gestation in the mouse, when the embryo contains six to seven pairs of somites, which are clusters of skeletal and muscle progenitors. The cells adopting the hepatic fate are characterized by the expression of two of the liver-specific markers, albumin and α-fetoprotein (AFP).
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