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First published online June 8, 2005
doi: 10.1242/10.1242/jcs.02403

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Three-dimensional polarization sensitizes hepatocytes to Fas/CD95 apoptotic signalling

¹ Institut de Génétique Moléculaire, CNRS UMR5535, IFR122, 1919 route de Mende, 34293 Montpellier Cedex 5, France
² UMR 5539 Centre National de la Recherche Scientifique, Dynamique Moléculaire des Interactions Membranaires, Université Montpellier II, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France
³ Service d'Anatomie Pathologique, Groupe Hospitalo-Universitaire Caremeau, Place du Pr Robert Debré, 30029 Nîmes Cedex 9, France
⁴ CRBM, CNRS FRE2593, IFR122, 1919 Route de Mende, 34293 Montpellier Cedex 5, France
⁵ UMR 5539 CNRS/UM2, IFR122, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France

^* Author for correspondence (e-mail: ula.hibner{at}igmm.cnrs.fr)

Accepted 23 March 2005

Maintenance of epithelial cell shape and polarity determines many vital cell functions, including the appropriate response to external stimuli. Murine hepatocytes cultured in a three-dimensional Matrigel matrix formed highly polarized organoids characterized by specific localization of an ERM (ezrin/radixin/moesin) protein, radixin, at microvillus-lined membrane domains. These apical domains surrounded a lumen and were bordered by tight junctions. The hepatocyte organoids were functional as judged by the high level of albumin secretion and accumulation of bilirubin. Stimulation of the Fas/CD95 death receptor, which is highly hepatotoxic in vivo, was a strong inducer of apoptosis in the polarized organoids. This was in sharp contrast to the monolayer hepatocyte cultures, which were protected from death by exacerbated NF-B signalling following engagement of the death receptors. Thus, hepatocytes in polarized, functional organoids modulate an intracellular signal transduction pathway, allowing the recapitulation of their physiological response to an apoptotic stimulus.

Key words: Apoptosis, Cell polarity, FAS/CD95, Hepatocyte, NF-B

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