sept7b is required for the differentiation of pancreatic endocrine progenitors
| Autor: | Dash, Surjya Narayan, Hakonen, Elina, Ustinov, Jarkko, Otonkoski, Timo, Andersson, Olov, Lehtonen, Sanna |
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| Přispěvatelé: | Medicum, Department of Pathology, Research Programs Unit, Research Programme for Molecular Neurology, Timo Pyry Juhani Otonkoski / Principal Investigator, Sanna Lehtonen research group |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty animal structures Cellular differentiation Morphogenesis Enteroendocrine cell Nerve Tissue Proteins Biology MOUSE Article Animals Genetically Modified 03 medical and health sciences Gene Knockout Techniques Islets of Langerhans SONIC-HEDGEHOG Internal medicine Insulin-Secreting Cells medicine Endocrine system Animals GLUCAGON Hedgehog Proteins Progenitor cell Sonic hedgehog Receptor Notch1 SPECIFICATION Zebrafish Homeodomain Proteins ORGANOGENESIS Multidisciplinary Gene Expression Regulation Developmental Cell Differentiation PRIMARY CILIUM Zebrafish Proteins biology.organism_classification Cell biology 030104 developmental biology medicine.anatomical_structure Endocrinology Glucagon-Secreting Cells CELLS MORPHOGENESIS biology.protein 3111 Biomedicine Endoderm Septins |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Protection or restoration of pancreatic β-cell mass as a therapeutic treatment for type 1 diabetes requires understanding of the mechanisms that drive the specification and development of pancreatic endocrine cells. Septins are filamentous small GTPases that function in the regulation of cell division, cytoskeletal organization and membrane remodeling and are involved in various tissue-specific developmental processes. However, their role in pancreatic endocrine cell differentiation remains unknown. Here we show by functional manipulation techniques in transgenic zebrafish lines that suppression of sept7b, the zebrafish ortholog of human SEPT7, profoundly increases the number of endocrine progenitors but limits their differentiation, leading to reduction in β- and α-cell mass. Furthermore, we discovered that shh (sonic hedgehog) expression in the endoderm, essential for the development of pancreatic progenitors of the dorsal pancreatic bud, is absent in larvae depleted of sept7b. We also discovered that sept7b is important for the differentiation of ventral pancreatic bud-derived cells: sept7b-depleted larvae exhibit downregulation of Notch receptors notch1a and notch1b and show precocious differentiation of NeuroD-positive endocrine cells in the intrapancreatic duct and gut epithelium. Collectively, this study provides a novel insight into the development of pancreatic endocrine progenitors, revealing an essential role for sept7b in endocrine progenitor differentiation. |
| Databáze: | OpenAIRE |
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