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Bile Duct Development and the Notch Signaling Pathway

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Alagille Syndrome

Abstract

Intrahepatic bile duct development is a sophisticated process that begins with a simple, perivenular arrangement of hepatoblasts and ends with an intricate, arborizing, hierarchical network of ducts that navigate the liver parenchyma, contributing to liver health and disease not only via drainage of bile but via direct and indirect interactions with surrounding cells. Development of the intrahepatic bile ducts depends upon cell specification and subsequent morphogenesis, both involving intercellular signaling through the Notch pathway. Alteration of this pathway by mutations in critical Notch ligands and/or Notch receptors disrupts normal intrahepatic bile duct formation and leads to the hepatobiliary phenotype seen in Alagille syndrome. More complete insight into the complexities of intrahepatic bile duct development and the signaling pathways involved (Notch and others) is a requisite preamble to defining cellular and molecular therapies with the potential of attenuating, or reversing, biliary injury in Alagille syndrome and other cholangiopathies.

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Authors and Affiliations

  1. Division of Gastroenterology Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Stacey S. Huppert & Kathleen M. Campbell

  2. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Stacey S. Huppert & Kathleen M. Campbell

Authors
  1. Stacey S. Huppert
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  2. Kathleen M. Campbell
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Correspondence to Stacey S. Huppert .

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Editors and Affiliations

  1. Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada

    Binita M. Kamath

  2. Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Kathleen M. Loomes

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Huppert, S.S., Campbell, K.M. (2018). Bile Duct Development and the Notch Signaling Pathway. In: Kamath, B., Loomes, K. (eds) Alagille Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-319-94571-2_2

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  • DOI: https://doi.org/10.1007/978-3-319-94571-2_2

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-94570-5

  • Online ISBN: 978-3-319-94571-2

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