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Vascular function and sphingosine-1-phosphate regulate development of the dorsal pancreatic mesenchyme

Författare:
  • Josefina Edsbagge
  • Jenny K Johansson
  • Farzad Esni
  • Yang Luo
  • Glenn L Radice
  • Henrik Semb
Publiceringsår: 2005
Språk: Engelska
Sidor: 1085-1092
Publikation/Tidskrift/Serie: Development
Volym: 132
Nummer: 5
Dokumenttyp: Artikel
Förlag: Company of Biologists

Sammanfattning

Early growth and differentiation of the pancreatic endoderm is regulated by soluble factors from the pancreatic mesenchyme. Previously, we demonstrated that N-cadherin-deficient mice lack a dorsal pancreas, due to a critical role of N-cadherin in dorsal pancreatic mesenchymal cell survival. Here, we show that restoring cardiac and circulatory function in N-cadherin null mice by cardiac-specific expression of N-cadherin, rescues formation of the dorsal pancreas, indicating that the phenotype is secondary to defects related to cardiac/vascular function. Based on this observation, we demonstrate that soluble factors present in plasma, such as sphingosine-1-phosphate, rescue formation of the dorsal pancreas in N-cadherin-deficient mice. We also show that sphingosine-1-phosphate indirectly promotes budding of the pancreatic endoderm by stimulating pancreatic mesenchymal cell proliferation. Finally, we identify sphingosine-1-phosphate receptors within the mesenchyme and show that pertussis toxin blocks the sphingosine-1-phosphate-induced actions, suggesting the involvement of G-protein-coupled sphingosine-1-phosphate receptors. Thus, we propose a new model where blood vessel-derived sphingosine-1-phosphate stimulates growth and budding of the dorsal pancreatic endoderm by induction of mesenchymal cell proliferation.

Disputation

Nyckelord

  • Medicine and Health Sciences
  • Mesenchyme
  • Mouse
  • Sphingosine-1-phosphate
  • Morphogenesis
  • Pancreas
  • Blood vessel

Övriga

Published
Yes
  • ISSN: 0950-1991

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