TY - JOUR
T1 - Morphogenesis of chicken liver
T2 - Identification of localized growth zones and the role of β-catenin/Wnt in size regulation
AU - Suksaweang, Sanong
AU - Lin, Chih Min
AU - Jiang, Ting Xin
AU - Hughes, Michael W.
AU - Widelitz, Randall B.
AU - Chuong, Cheng Ming
N1 - Funding Information:
We thank Mr. David Huang for help in this work and Ms. Maji Ramos and Fiona McCulloch for the preparation of the manuscript; Dr. Neil Kaplowitz and Dr. Hide Tsukamoto for constructive comments and support; and Joe Lin and Zhicao Yue for discussions in solving technical problems. We are grateful to Dr. Randy Johnson for RCAS β-catenin, Dr. Tabin for DN-LEF1, Dr. Andrew Lassar and Dr. Sarah Millar for DKK, and Dr. William Pavan for RCAS Gateway cloning vector. This study was supported by grants from NIDDK P30 DK048522 (the USC Research Center for Liver Diseases), NIH AR42177, AR47364 (CMC), and NCI CA83716 (RW). Sanong Suksaweang is supported by the Royal Thai Government Scholarship from Thailand.
PY - 2004/2/1
Y1 - 2004/2/1
N2 - During development and regeneration, new cells are added and incorporated to the liver parenchyma. Regulation of this process contributes to the final size and shape of the particular organs, including the liver. We identified the distribution of liver growth zones using an embryonic chicken model because of its accessibility to experimentation. Hepatocyte precursors were first generated all over the primordia surrounding the vitelline blood vessel at embryonic day 2 (E2), then became limited to the peripheral growth zones around E6. Differentiating daughter cells of the peripheral hepatocyte precursors were shown by DiI microinjection to be laid inward and were subsequently organized to form the hepatic architecture. At E8, hepatocyte precursor cells were further restricted to limited segments of the periphery, called localized growth zones (LoGZ). Adhesion and signaling molecules in the growth zone were studied. Among them, β-catenin and Wnt 3a were highly enriched. We overexpressed constitutively active β-catenin using replication competent avian sarcoma (RCAS) virus. Liver size increased about 3-fold with an expanded hepatocyte precursor cell population. In addition, blocking β-catenin activity by either overexpression of dominant-negative LEF1 or overexpression of a secreted Wnt inhibitor Dickkopf (DKK) resulted in decreased liver size with altered liver shape. Our data suggest that (1) the duration of active growth zone activity modulates the size of the liver; (2) a shift in the position of the localized growth zone helps to shape the liver; and (3) β-catenin/Wnt are involved in regulating growth zone activities during liver development.
AB - During development and regeneration, new cells are added and incorporated to the liver parenchyma. Regulation of this process contributes to the final size and shape of the particular organs, including the liver. We identified the distribution of liver growth zones using an embryonic chicken model because of its accessibility to experimentation. Hepatocyte precursors were first generated all over the primordia surrounding the vitelline blood vessel at embryonic day 2 (E2), then became limited to the peripheral growth zones around E6. Differentiating daughter cells of the peripheral hepatocyte precursors were shown by DiI microinjection to be laid inward and were subsequently organized to form the hepatic architecture. At E8, hepatocyte precursor cells were further restricted to limited segments of the periphery, called localized growth zones (LoGZ). Adhesion and signaling molecules in the growth zone were studied. Among them, β-catenin and Wnt 3a were highly enriched. We overexpressed constitutively active β-catenin using replication competent avian sarcoma (RCAS) virus. Liver size increased about 3-fold with an expanded hepatocyte precursor cell population. In addition, blocking β-catenin activity by either overexpression of dominant-negative LEF1 or overexpression of a secreted Wnt inhibitor Dickkopf (DKK) resulted in decreased liver size with altered liver shape. Our data suggest that (1) the duration of active growth zone activity modulates the size of the liver; (2) a shift in the position of the localized growth zone helps to shape the liver; and (3) β-catenin/Wnt are involved in regulating growth zone activities during liver development.
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U2 - 10.1016/j.ydbio.2003.10.010
DO - 10.1016/j.ydbio.2003.10.010
M3 - Article
C2 - 14729482
AN - SCOPUS:0345830410
VL - 266
SP - 109
EP - 122
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 1
ER -