Genetic determinants of pancreatic ε-cell development
| Autor: | Patrick Collombat, Ole D. Madsen, Gérard Gradwohl, Marjorie Jenny, Ahmed Mansouri, R S Heller, Palle Serup, Georg Mellitzer, Catherine Tomasetto |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
endocrine system
medicine.medical_specialty Cell type Pancreas morphogenesis 030209 endocrinology & metabolism Enteroendocrine cell Development Biology Glucagon 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Pancreas Molecular Biology 030304 developmental biology Pax4 0303 health sciences digestive oral and skin physiology Cell Biology Ghrelin Pax6 Endocrinology medicine.anatomical_structure Neurogenin3 Epsilon cell PAX4 Arx Endocrine hormones hormone substitutes and hormone antagonists Developmental Biology |
| Zdroj: | Developmental Biology. 286:217-224 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2005.06.041 |
| Popis: | Recently, the expression of the peptide hormone ghrelin was detected in alpha-cells of the islets of Langerhans as well as in epsilon-cells, a newly discovered endocrine cell type, but it remains unclear how the latter is related in lineage to the four classical islet cell types, alpha-, beta-, delta-, and PP-cells. Here, we provide further evidence that ghrelin is predominantly produced in the alpha-cells of mouse islets but also in single hormone ghrelin-secreting epsilon-cells. We additionally demonstrate that pancreatic epsilon-cells derive from Neurogenin3-expressing precursor cells and their genesis depends on Neurogenin3 activity. Furthermore, our data indicate that the number of ghrelin-producing cells is differentially regulated during pancreas morphogenesis by the homeodomain-containing transcription factors Arx, Pax4, and Pax6. Arx mutants lack ghrelin+ glucagon+ alpha-cells whereas Pax4 mutants develop an excess of these cells. Importantly, the ghrelin+ glucagon- epsilon-cell population is not affected following Arx or Pax4 disruption. In contrast, the loss of Pax6 provokes an unexpected increase of the ghrelin+ glucagon- epsilon-cell number which is not due to increased proliferation. Thus, we demonstrate that the development of ghrelin-producing cells is differentially dependent on Neurogenin3 in different domains of the gastrointestinal tract and that, in the endocrine pancreas, epsilon-cell genesis does not require Arx or Pax4 activities but is antagonized by Pax6. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect