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Ngn3+ endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium
- Source :
- Developmental Biology; Vol 359
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- During pancreas development, endocrine and exocrine cells arise from a common multipotent progenitor pool. How these cell fate decisions are coordinated with tissue morphogenesis is poorly understood. Here we have examined ductal morphology, endocrine progenitor cell fate and Notch signaling in Ngn3−/− mice, which do not produce islet cells. Ngn3 deficiency results in reduced branching and enlarged pancreatic duct-like structures, concomitant with Ngn3 promoter activation throughout the ductal epithelium and reduced Notch signaling. Conversely, forced generation of surplus endocrine progenitor cells causes reduced duct caliber and an excessive number of tip cells. Thus, endocrine progenitor cells normally provide a feedback signal to adjacent multipotent ductal progenitor cells that activates Notch signaling, inhibits further endocrine differentiation and promotes proper morphogenesis. These results uncover a novel layer of regulation coordinating pancreas morphogenesis and endocrine/exocrine differentiation, and suggest ways to enhance the yield of beta cells from stem cells.
- Subjects :
- medicine.medical_specialty
Notch
Morphogenesis
Notch signaling pathway
Pancreas morphogenesis
Mice, Transgenic
Nerve Tissue Proteins
Biology
Lineage tracing
Article
Mice
03 medical and health sciences
0302 clinical medicine
Internal medicine
Basic Helix-Loop-Helix Transcription Factors
Branching morphogenesis
medicine
Animals
Pancreas development
Cell Lineage
Lateral inhibition
Progenitor cell
Molecular Biology
030304 developmental biology
Progenitor
0303 health sciences
Pancreatic Ducts
Epithelial Cells
Cell Biology
Cell biology
Endothelial stem cell
Endocrinology
medicine.anatomical_structure
Jagged1
Neurogenin3
Stem cell
Pancreas
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- ISSN :
- 00121606
- Volume :
- 359
- Database :
- OpenAIRE
- Journal :
- Developmental Biology
- Accession number :
- edsair.doi.dedup.....4b1fb75e24ea8e01e9a5ce3e0794ba10