Two transgenic approaches to define the cell lineages in endocrine pancreas development.
Ontogenic relationships between the different endocrine cell types of the islets of Langerhans were explored by generating transgenic mice, in which cells transcribing the glucagon, insulin, or pancreatic polypeptide genes were destroyed through the promoter-targeted expression of the diphtheria toxin A chain. In an alternate approach, to assess whether insulin cells are derived from precursors producing glucagon or PP, transgenic mice were generated bearing an insulin promoter-driven, and loxP-containing ('floxed') reporter transgene that can be irreversibly 'tagged' by recombination. They were crossed with mice expressing another transgene ('tagger') encoding Cre (cyclization recombination) recombinase in either glucagon or PP cells. The results obtained using both approaches indicate that neither glucagon nor insulin gene-expressing cells are the precursors to the other islet cells; also, they suggest that PP gene-expressing cells are necessary for the differentiation of islet insulin and somatostatin cells, through a cell lineage or a paracrine relationship.
Department of Morphology, Faculty of Medicine, Geneva, Switzerland.
P L
PL
Herrera
L
L
Orci
J D
JD
Vassalli
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D004167:Diphtheria Toxin / Q000235:genetics / Q000633:toxicity; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D019426:Integrases / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology* / Q000254:growth & development; D051379:Mice; D008822:Mice, Transgenic; D010187:Pancreatic Hormones / Q000096:biosynthesis / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics / Q000633:toxicity; D011995:Recombination, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D013234:Stem Cells / Q000166:cytology; D019076:Transgenes / Q000235:genetics*; D014764:Viral Proteins
D004167:Diphtheria Toxin; D010187:Pancreatic Hormones; D010446:Peptide Fragments; D014764:Viral Proteins; C029795:diphtheria toxin fragment A; C045073:Cre recombinase; D019426:Integrases