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1 - Liver Development: From Endoderm to Hepatocyte

from SECTION I - PATHOPHYSIOLOGY OF PEDIATRIC LIVER DISEASE

Published online by Cambridge University Press:  18 December 2009

By
Torsten Wuestefeld Ph.D.  and
Kenneth S. Zaret Ph.D.
Edited by
Frederick J. Suchy ,
Ronald J. Sokol  and
William F. Balistreri
Torsten Wuestefeld Ph.D.
Affiliation:
Postdoctoral Fellow, Cell and Developmental Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania
Kenneth S. Zaret Ph.D.
Affiliation:
Senior Member and Program Leader, Cell and Developmental Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania
Frederick J. Suchy
Affiliation:
Mount Sinai School of Medicine, New York
Ronald J. Sokol
Affiliation:
University of Colorado, Denver
William F. Balistreri
Affiliation:
University of Cincinnati
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Summary

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).

Type
Chapter
Information
Liver Disease in Children , pp. 3 - 13
Publisher: Cambridge University Press
Print publication year: 2007

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