Hepatocyte nuclear factor 4alpha orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver.
Epithelial formation is a central facet of organogenesis that relies on intercellular junction assembly to create functionally distinct apical and basal cell surfaces. How this process is regulated during embryonic development remains obscure. Previous studies using conditional knockout mice have shown that loss of hepatocyte nuclear factor 4alpha (HNF4alpha) blocks the epithelial transformation of the fetal liver, suggesting that HNF4alpha is a central regulator of epithelial morphogenesis. Although HNF4alpha-null hepatocytes do not express E-cadherin (also called CDH1), we show here that E-cadherin is dispensable for liver development, implying that HNF4alpha regulates additional aspects of epithelial formation. Microarray and molecular analyses reveal that HNF4alpha regulates the developmental expression of a myriad of proteins required for cell junction assembly and adhesion. Our findings define a fundamental mechanism through which generation of tissue epithelia during development is coordinated with the onset of organ function.
Battle
Michele A
MA
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226-0509, USA.
Konopka
Genevieve
G
Parviz
Fereshteh
F
Gaggl
Alexandra Lerch
AL
Yang
Chuhu
C
Sladek
Frances M
FM
Duncan
Stephen A
SA
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051557:Hepatocyte Nuclear Factor 4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007365:Intercellular Junctions / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission
D015820:Cadherins; D015815:Cell Adhesion Molecules; D051557:Hepatocyte Nuclear Factor 4