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

Edsbagge, Josefina; Johansson, Jenny K; Esni, Farzad; Luo, Yang; Radice, Glenn L and Semb, Henrik LU (2005) In Development 132(5). p.1085-1092
Abstract
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... (More)
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. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Mesenchyme, Mouse, Sphingosine-1-phosphate, Morphogenesis, Pancreas, Blood vessel
in
Development
volume
132
issue
5
pages
1085 - 1092
publisher
Society for International Development
external identifiers
  • pmid:15689381
  • scopus:16844375322
ISSN
1477-9129
DOI
10.1242/dev.01643
language
English
LU publication?
no
id
ab252455-b57d-487b-871f-e0062a27c03a (old id 1134259)
date added to LUP
2008-06-18 09:32:48
date last changed
2017-11-12 03:32:10
@article{ab252455-b57d-487b-871f-e0062a27c03a,
  abstract     = {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.},
  author       = {Edsbagge, Josefina and Johansson, Jenny K and Esni, Farzad and Luo, Yang and Radice, Glenn L and Semb, Henrik},
  issn         = {1477-9129},
  keyword      = {Mesenchyme,Mouse,Sphingosine-1-phosphate,Morphogenesis,Pancreas,Blood vessel},
  language     = {eng},
  number       = {5},
  pages        = {1085--1092},
  publisher    = {Society for International Development},
  series       = {Development},
  title        = {Vascular function and sphingosine-1-phosphate regulate development of the dorsal pancreatic mesenchyme},
  url          = {http://dx.doi.org/10.1242/dev.01643},
  volume       = {132},
  year         = {2005},
}