FGF signaling segregates biliary cell-lineage from chick hepatoblasts cooperatively with BMP4 and ECM components in vitro.
Intrahepatic bile ducts (IHBDs) are indispensable for transporting bile secreted from hepatocytes to the hepatic duct. The biliary epithelial cells (BECs) of the IHBD arise from bipotent hepatoblasts around the portal vein, suggesting the portal mesenchyme is essential for their development. However, except for Notch or Activin/TGF-beta signaling molecules, it is not known which molecules regulate IHBD development. Here, we found that FGF receptors and BMP4 are specifically expressed in the developing IHBD and the hepatic mesenchyme, respectively. Using a mesenchyme-free culture of liver bud, we showed that bFGF and FGF7 induce the hepatoblasts to differentiate into BECs, and that BMP4 enhances bFGF-induced BEC differentiation. The extracellular matrix (ECM) components in the hepatic mesenchyme induced BEC differentiation. Forced expression of a constitutively active form of the FGF receptor partially induced BEC differentiation markers in vivo. These data strongly suggest that bFGF and FGF7 promote BEC differentiation cooperatively with BMP4 and ECMs in vivo.
Yanai
Masaaki
M
Division of Pattern Formation, Department of Organogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Tatsumi
Norifumi
N
Hasunuma
Noboru
N
Katsu
Kenjiro
K
Endo
Fumio
F
Yokouchi
Yuji
Y
D000818:Animals; D001652:Bile Ducts / Q000033:anatomy & histology / Q000502:physiology; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D002478:Cells, Cultured; D002645:Chickens; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D053539:Keratin-19 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000502:physiology; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D009024:Morphogenesis; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; D053539:Keratin-19; D017468:Receptors, Fibroblast Growth Factor; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; D051523:Fibroblast Growth Factor 7; D017228:Hepatocyte Growth Factor