Dicer is required for proper liver zonation
Article first published online: 27 JUL 2009
Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 219, Issue 3, pages 365–372, November 2009
How to Cite
Sekine, S., Ogawa, R., Mcmanus, M. T., Kanai, Y. and Hebrok, M. (2009), Dicer is required for proper liver zonation. J. Pathol., 219: 365–372. doi: 10.1002/path.2606
- Issue published online: 9 OCT 2009
- Article first published online: 27 JUL 2009
- Accepted manuscript online: 27 JUL 2009 12:00AM EST
- Manuscript Revised: 17 JUL 2009
- Manuscript Accepted: 17 JUL 2009
- Manuscript Received: 21 JUN 2009
- KAKENHI. Grant Number: 20790315
- NIH. Grant Number: CA112537
A number of genes and their protein products are expressed within the liver lobules in a region-specific manner and confer heterogeneous metabolic properties to hepatocytes; this phenomenon is known as ‘metabolic zonation’. To elucidate the roles of Dicer, an endoribonuclease III type enzyme required for microRNA biogenesis, in the establishment of liver zonation, we examined the distribution of proteins exhibiting pericentral or periportal localization in hepatocyte-specific Dicer1 knockout mouse livers. Immunohistochemistry showed that the localization of pericentral proteins was mostly preserved in Dicer1-deficient livers. However, glutamine synthetase, whose expression is normally confined to a few layers of hepatocytes surrounding the central veins, was expressed in broader pericentral areas. Even more striking was the observation that all the periportal proteins that were examined, including phosphoenolpyruvate carboxykinase, E-cadherin, arginase 1, and carbamoyl phosphate synthetase-I, lost their localized expression patterns and were diffusely expressed throughout the entire lobule. Thus, with regard to periportal protein expression, the consequences of Dicer loss were similar to those caused by the disruption of β-catenin. An analysis of livers deficient in β-catenin did not identify the down-regulation of Dicer1 or any microRNAs, indicating that they are not directly activated by β-catenin. Thus, the present study illustrates that Dicer plays a pivotal role in the establishment of liver zonation. Dicer is essential for the suppression of periportal proteins by Wnt/β-catenin/TCF signalling, albeit it likely acts in an indirect manner. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.