Reiterative use of the notch signal during zebrafish intrahepatic biliary development.
The Notch signaling pathway regulates specification of zebrafish liver progenitor cells towards a biliary cell fate. Here, using staged administration of a pharmacological inhibitor of Notch receptor processing, we show that activation of the Notch pathway is also important for growth and expansion of the intrahepatic biliary network in zebrafish larvae. Biliary expansion is accompanied by extensive cell proliferation and active remodeling of the nascent ductal network, as revealed by time lapse imaging of living zebrafish larvae that express a Notch responsive fluorescent reporter transgene. Together, these data support a model in which the Notch signal functions reiteratively during biliary development; first to specific biliary cells and then to direct remodeling of the nascent biliary network. As the Notch pathway plays a comparable role during mammalian biliary development, including humans, these studies also indicate broad conservation of the molecular mechanisms directing biliary development in vertebrates.
Lorent
Kristin
K
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19130, USA.
Moore
John C
JC
Siekmann
Arndt F
AF
Lawson
Nathan
N
Pack
Michael
M
D000818:Animals; D001652:Bile Ducts / Q000196:embryology*; D019070:Cell Lineage; D049109:Cell Proliferation; D005456:Fluorescent Dyes / Q000737:chemistry; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000196:embryology; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D019076:Transgenes; D015027:Zebrafish
D005456:Fluorescent Dyes; D051880:Receptors, Notch