The competency of foregut mesenchyme in islet mesenchyme-to-epithelial transition during embryonic development.
OBJECTIVE
Potential for curative stem-cell treatments of juvenile-onset diabetes has focussed research into pancreatic islet development. Islets were previously thought to originate solely from embryonic pancreatic epithelium, but we have demonstrated that islets can originate from mesenchyme, that is, islet mesenchyme-to-epithelial transition. The aim of this study was to establish the competence of foregut mesenchyme during mesenchymal islet development.


METHODS
Embryonic chick pancreatic epithelium of gestational stage Hamburger-Hamilton (HH) 22 (J Morphol. 1951;88:49-92) was combined with quail stomach mesenchyme of increasing gestation (stage HH22 [n = 6], HH26 [n = 6], HH28 [n = 4], or HH31 [n = 6]). Recombinants were cultured and analysed by immunocytochemistry for coexpression of insulin and quail-specific antigen to determine the embryonic origin of islets.


RESULTS
Recombinants constructed using stage HH22 mesenchyme yielded 34 islets, of which 35% were mesenchymal. However, when recombinants were constructed using stage HH26 mesenchyme, 24% of 25 islets were mesenchymal. When using mesenchyme, 13% of 15 islets were mesenchymal. All islets (n = 35) in recombinants constructed using stage HH31 mesenchyme were epithelial derived. Islet mesenchyme-to-epithelial transition diminished significantly with increasing mesenchymal gestational stage (P = .002).


CONCLUSIONS
These data show foregut mesenchyme is competent to form islets between stages HH22 and HH28. Developmental competence of foregut mesenchyme in islet mesenchyme-to-epithelial transition diminishes as gestation increases. This may have important implications for identifying stem cells to treat juvenile-onset diabetes.
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, OX3 9DU Oxford, United Kingdom. warwick.teague@nds.ox.ac.uk
Warwick J
WJ
Teague
Autumn M
AM
Rowan-Hull
Naga V G
NV
Jayanthi
Paul R V
PR
Johnson
D000818:Animals; D002642:Chick Embryo; D004848:Epithelium / Q000196:embryology*; D007515:Islets of Langerhans / Q000196:embryology*; D008648:Mesoderm; D011784:Quail / Q000196:embryology