Retinoic acid signaling is essential for pancreas development and promotes endocrine at the expense of exocrine cell differentiation in Xenopus

Dev Biol. 2004 Jul 1;271(1):144-60. doi: 10.1016/j.ydbio.2004.03.030.


How and when the vertebrate endoderm is first subdivided into discrete progenitor cell populations that will give rise to the different major organs, including pancreas and liver, are only poorly understood. We have used Xenopus laevis as a model system to characterize these events, since it is particularly suited to study the early embryonic patterning in vertebrates. Our experimental results support the notion that retinoic acid (RA) functions as an essential endodermal patterning signal in Xenopus and that it acts as early as during gastrulation. As a result of RA treatment, the expression of Sonic Hedgehog (Shh), a known inhibitor of pancreas development in other vertebrate systems, is negatively regulated in the dorsal prepancreatic endoderm. Furthermore, RA is found to promote endocrine at the expense of exocrine differentiation in the dorsal pancreas, correlating with a specific inhibition of Notch signaling activities in this territory. Conversely, RA enhances exocrine marker gene expression in the ventral pancreas.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Cell Differentiation / physiology*
  • DNA Primers
  • Endoderm / physiology
  • Enteroendocrine Cells / physiology
  • Epigenesis, Genetic*
  • Exocrine Glands / embryology
  • Hedgehog Proteins
  • In Situ Hybridization
  • Insulin / metabolism
  • Microinjections
  • Morphogenesis
  • Pancreas / embryology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • T-Box Domain Proteins / metabolism
  • Trans-Activators / metabolism
  • Tretinoin / metabolism
  • Tretinoin / physiology*
  • Xenopus Proteins*
  • Xenopus laevis


  • DNA Primers
  • Hedgehog Proteins
  • Insulin
  • T-Box Domain Proteins
  • Trans-Activators
  • VegT protein, Xenopus
  • Xenopus Proteins
  • Tretinoin