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Identifier

000379205

Title

Λειτουργική ανάλυση νέων γονιδίων που εμπλέκονται στη διαφοροποίηση της ενδοκρινούς μοίρας του παγκρέατος

Alternative Title

Functional analysis of novel genes implicated in endocrine pancreas development

Author

Ιωάννου, Μαρίλια Κ

Thesis advisor

Μαυροθαλασσίτης, Γεώργιος

Reviewer

Γαβαλάς, Αντώνης
Καραγωγέως, Δόμνα
Καρδάσης, Δημήτριος
Παπαματθαιάκης, Ιωσήφ
Αλεξανδράκη, Δέσποινα
Χαλεπάκης, Γεώργιος

Abstract

The aim of this thesis was the identification and functional analysis of novel genes, targets of Ngn3, implicated in endocrine pancreas development. In a screen conducted for downstream Ngn3 target genes using ES derived pancreas progenitors we identified Aldh1b1, encoding a mitochondrial enzyme, as one of the genes strongly upregulated in response to Ngn3 expression. Aldehydedehydrogenase (ALDH) genes are increasingly associated with stem/progenitor cell status but their role in the maintenance of pluripotency remains uncertain. We found both in situ hybridization and immunofluorescence using a specific antibody that ALDH1B1 is exclusively expressed in the emerging pancreatic buds of the early embryo (9.5dpc) in a Pdx1 dependet manner. Around the time of secondary transition, ALDH1B1 expression was restricted in the tiptri potent progenitors of the branching epithelium and in a subset of the trunk epithelium. Expression in the later was NGN3 dependent. Subsequently, ALDH1B1 expression persistent only in the tip cells tha become restricted to the exocrine lineage declined rapidly as these cells mature. In the adult pancres we identified rare ALDH1B1 cells tha become abundant following pancreas injury in mice injected with cerulein (for acinar cell destruction) or streptozotocin (for beta cell destruction). Moreover blocking ALDH catalytic activity in embryonic pancreas explants in culture resulted in reduced size of the explants and accelerated differentiation suggesting for the firts time tha ALDH activity may be necessary in the develping pancreas for the maintenace and axpansion of progenitor pools.

Language

Greek, English

Subject

ALDH1B1

Aldehydedehydrogenase

Centroacinar cells

Genetic Phenomena

Molecular Biology

NGN3

PDX1

Pancreas regeneration

Pancreas stem and progenitor cells