Open Access Highly Accessed Research article

Mechanism of primitive duct formation in the pancreas and submandibular glands: a role for SDF-1

Anne-Christine Hick1†, Jonathan M van Eyll1†, Sabine Cordi1, Céline Forez1, Lara Passante2, Hiroshi Kohara3, Takashi Nagasawa3, Pierre Vanderhaeghen2, Pierre J Courtoy1, Guy G Rousseau1, Frédéric P Lemaigre1 and Christophe E Pierreux1*

Author Affiliations

1 Université catholique de Louvain, de Duve Institute, 75 Avenue Hippocrate, B-1200 Brussels, Belgium

2 Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Free University of Brussels, 808 Route de Lennik, B-1070 Brussels, Belgium

3 Institute for Frontier Medical Science, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 Japan

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BMC Developmental Biology 2009, 9:66 doi:10.1186/1471-213X-9-66

Published: 14 December 2009

Abstract

Background

The exocrine pancreas is composed of a branched network of ducts connected to acini. They are lined by a monolayered epithelium that derives from the endoderm and is surrounded by mesoderm-derived mesenchyme. The morphogenic mechanisms by which the ductal network is established as well as the signaling pathways involved in this process are poorly understood.

Results

By morphological analyzis of wild-type and mutant mouse embryos and using cultured embryonic explants we investigated how epithelial morphogenesis takes place and is regulated by chemokine signaling. Pancreas ontogenesis displayed a sequence of two opposite epithelial transitions. During the first transition, the monolayered and polarized endodermal cells give rise to tissue buds composed of a mass of non polarized epithelial cells. During the second transition the buds reorganize into branched and polarized epithelial monolayers that further differentiate into tubulo-acinar glands. We found that the second epithelial transition is controlled by the chemokine Stromal cell-Derived Factor (SDF)-1. The latter is expressed by the mesenchyme, whereas its receptor CXCR4 is expressed by the epithelium. Reorganization of cultured pancreatic buds into monolayered epithelia was blocked in the presence of AMD3100, a SDF-1 antagonist. Analyzis of sdf1 and cxcr4 knockout embryos at the stage of the second epithelial transition revealed transient defective morphogenesis of the ventral and dorsal pancreas. Reorganization of a globular mass of epithelial cells in polarized monolayers is also observed during submandibular glands development. We found that SDF-1 and CXCR4 are expressed in this organ and that AMD3100 treatment of submandibular gland explants blocks its branching morphogenesis.

Conclusion

In conclusion, our data show that the primitive pancreatic ductal network, which is lined by a monolayered and polarized epithelium, forms by remodeling of a globular mass of non polarized epithelial cells. Our data also suggest that SDF-1 controls the branching morphogenesis of several exocrine tissues.