Cytokinesis defines a spatial landmark for hepatocyte polarization and apical lumen formation.
By definition, all epithelial cells have apical-basal polarity, but it is unclear how epithelial polarity is acquired and how polarized cells engage in tube formation. Here, we show that hepatocyte polarization is linked to cytokinesis using the rat hepatocyte cell line Can 10. Before abscission, polarity markers are delivered to the site of cell division in a strict spatiotemporal order. Immediately after abscission, daughter cells remain attached through a unique disc-shaped structure, which becomes the site for targeted exocytosis, resulting in the formation of a primitive bile canaliculus. Subsequently, oriented cell division and asymmetric cytokinesis occur at the bile canaliculus midpoint, resulting in its equal partitioning into daughter cells. Finally, successive cycles of oriented cell division and asymmetric cytokinesis lead to the formation of a tubular bile canaliculus, which is shared by two rows of hepatocytes. These findings define a novel mechanism for cytokinesis-linked polarization and tube formation, which appears to be broadly conserved in diverse cell types.
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ting
T
Wang
Gastroenterology Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kilangsungla
K
Yanger
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Gastroenterology Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ben Z
BZ
Stanger
INSERM, UMR-S 757, Université Paris-Sud, Orsay, F-91405, France.
Doris
D
Cassio
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA ebi@mail.med.upenn.edu.
Erfei
E
Bi
D000818:Animals; D001648:Bile Canaliculi / Q000166:cytology*; D015415:Biomarkers / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D016764:Cell Polarity; D048749:Cytokinesis; D004847:Epithelial Cells / Q000502:physiology*; D022781:Hepatocytes / Q000502:physiology*; D008565:Membrane Proteins; D009024:Morphogenesis / Q000235:genetics; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats
D015415:Biomarkers; D002352:Carrier Proteins; C076326:Exoc4 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C472451:Pard3 protein, rat; D034741:RNA, Small Interfering
Apical tube formation; Cytokinesis; Exocyst; Hepatocyte; Par3; Polarization