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Published 18 December 2006. doi:10.1083/jcb.200608012
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 175, Number 6, 971-980
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Article

The nuclear receptor hepatocyte nuclear factor 4{alpha} acts as a morphogen to induce the formation of microvilli



Hideki Chiba1, Naoyuki Sakai1, Masaki Murata1, Makoto Osanai1, Takafumi Ninomiya2, Takashi Kojima1, and Norimasa Sawada1

1 Department of Pathology and 2 Department of Anatomy, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan

Correspondence to Hideki Chiba: hidchiba{at}sapmed.ac.jp

Microvilli are actin-based organelles found on apical plasma membranes that are involved in nutrient uptake and signal transduction. Numerous components, including ezrin/radixin/moesin (ERM) proteins, have been identified that link filamentous actins to transmembrane proteins, but the signals driving microvillus biogenesis are not known. In this study, we show that the conditional and/or ectopic expression of a nuclear receptor, hepatocyte nuclear factor 4{alpha} (HNF4{alpha}), triggers microvillus morphogenesis. We also demonstrate that HNF4{alpha} expression induces ERM-binding phosphoprotein 50 (EBP50) expression and that attenuation of EBP50 using RNA interference inhibits microvillus development. We conclude that HNF4{alpha} acts as a morphogen to trigger microvillus formation.

Abbreviations used in this paper: Dox, doxycycline; EBP50, ERM-binding phosphoprotein 50; ERM, ezrin/radixin/moesin; HNF4{alpha}, hepatocyte nuclear factor 4{alpha}; RAR{gamma}, retinoic acid receptor {gamma}; RLE, rat lung endothelial; RXR{alpha}, retinoid X receptor {alpha}; tRA, all-trans retinoic acid; WT, wild type.


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