TY - JOUR
T1 - Ablation of islet endocrine cells by targeted expression of hormone-promoter-driven toxigenes
AU - Herrera, Pedro Luis
AU - Huarte, Joaquin
AU - Zufferey, Romain
AU - Nichols, Anthony
AU - Mermillod, Bernadette
AU - Philippe, Jacques
AU - Muniesa, Pedro
AU - Sanvito, Francesca
AU - Orci, Lelio
AU - Vassalli, Jean Dominique
PY - 1994/12/20
Y1 - 1994/12/20
N2 - Ontogenic relationships between the different types of endocrine cells in the islets of Langerhans were explored by generating transgenic mouse embryos in which cells transcribing the glucagon, insulin, or pancreatic polypeptide genes were destroyed through the promoter-targeted expression of the diphtheria toxin A chain. Embryos lacking glucagon- or insulin-containing cells did not exhibit alterations in the development of the nontargeted islet cell types, whereas embryos lacking pancreatic polypeptide gene-expressing cells also lacked pancreatic insulin- and somatostatin-containing cells. These results show that neither glucagon nor insulin gene-expressing cells are essential for the differentiation of the other islet endocrine-cell types. These results also suggest that pancreatic polypeptide gene-expressing cells are indispensable for the differentiation of islet β and δ cells because the former produce a necessary paracrine or endocrine factor and/or operate through a cell-lineage relationship.
AB - Ontogenic relationships between the different types of endocrine cells in the islets of Langerhans were explored by generating transgenic mouse embryos in which cells transcribing the glucagon, insulin, or pancreatic polypeptide genes were destroyed through the promoter-targeted expression of the diphtheria toxin A chain. Embryos lacking glucagon- or insulin-containing cells did not exhibit alterations in the development of the nontargeted islet cell types, whereas embryos lacking pancreatic polypeptide gene-expressing cells also lacked pancreatic insulin- and somatostatin-containing cells. These results show that neither glucagon nor insulin gene-expressing cells are essential for the differentiation of the other islet endocrine-cell types. These results also suggest that pancreatic polypeptide gene-expressing cells are indispensable for the differentiation of islet β and δ cells because the former produce a necessary paracrine or endocrine factor and/or operate through a cell-lineage relationship.
KW - Cell lineage
KW - Diphtheria toxin
KW - Pancreas
KW - Pancreatic polypeptide-fold family
KW - Transgenic
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M3 - Article
C2 - 7809163
AN - SCOPUS:0028559916
VL - 91
SP - 12999
EP - 13003
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 26
ER -