Journal ArticleDOI
The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors
Yoshiya Kawaguchi,Bonnie Cooper,Maureen Gannon,Michael Ray,Raymond J. MacDonald,Christopher V.E. Wright +5 more
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TLDR
Rec recombination-based lineage tracing in vivo is used to show that PTF1a is expressed at these early stages in the progenitors of pancreatic ducts, exocrine and endocrine cells, rather than being an exocrine-specific gene as previously described.Abstract:
Pancreas development begins with the formation of buds at specific sites in the embryonic foregut endoderm. We used recombination-based lineage tracing in vivo to show that Ptf1a (also known as PTF1-p48) is expressed at these early stages in the progenitors of pancreatic ducts, exocrine and endocrine cells, rather than being an exocrine-specific gene as previously described. Moreover, inactivation of Ptf1a switches the character of pancreatic progenitors such that their progeny proliferate in and adopt the normal fates of duodenal epithelium, including its stem-cell compartment. Consistent with the proposal that Ptf1a supports the specification of precursors of all three pancreatic cell types, transgene-based expression of Pdx1, a gene essential to pancreas formation, from Ptf1a cis-regulatory sequences restores pancreas tissue to Pdx1-null mice that otherwise lack mature exocrine and endocrine cells because of an early arrest in organogenesis. These experiments provide evidence that Ptf1a expression is specifically connected to the acquisition of pancreatic fate by undifferentiated foregut endoderm.read more
Citations
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Origin of exocrine pancreatic cells from nestin-positive precursors in developing mouse pancreas
TL;DR: It is demonstrated that a nestin promoter/enhancer element containing the second intron of the mouse nestin locus is active in undifferentiated E10.5 pancreatic epithelial cells, and that these nestin-positive precursors contribute to the generation of differentiated acinar cells.
Journal ArticleDOI
Cellular and molecular mechanisms coordinating pancreas development.
TL;DR: The developmental mechanisms and principles that are known to underlie pancreas development, from induction and lineage formation to morphogenesis and organogenesis are discussed.
Journal ArticleDOI
Dissecting the Role of Glucocorticoids on Pancreas Development
Emilie Gesina,François Tronche,Pedro Luis Herrera,B. Duchene,Willemene Tales,Paul Czernichow,Bernadette Breant +6 more
TL;DR: It is demonstrated that glucocorticoids play an important role in pancreatic beta-cell lineage, acting before hormone gene expression onset and possibly also modulating the balance between endocrine and exocrine cell differentiation.
Journal ArticleDOI
Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb
Tomoko Kuwabara,Mohamedi N. Kagalwala,Yasuko Onuma,Yuzuru Ito,Masaki Warashina,Masaki Warashina,Kazuyuki Terashima,Tsukasa Sanosaka,Kinichi Nakashima,Fred H. Gage,Makoto Asashima +10 more
TL;DR: This study demonstrated that insulin is produced not only in the mammalian pancreas but also in adult neuronal cells derived from the hippocampus and olfactory bulb, and indicated that the balance between Wnt3, which triggers the expression of insulin via NeuroD1, and IGFBP‐4, which inhibits the original Wnt 3 action, is regulated depending on diabetic (DB) status.
Journal ArticleDOI
The molecular and morphogenetic basis of pancreas organogenesis.
TL;DR: The understanding of pancreas development in model organisms provides a framework to interpret how human mutations lead to neonatal diabetes and may contribute to other forms of diabetes and to guide the production of desired pancreatic cell types from pluripotent stem cells for therapeutic purposes.
References
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Journal ArticleDOI
Insulin-promoter-factor 1 is required for pancreas development in mice
TL;DR: The findings show that IPF1 is needed for the formation of the pancreas and suggest that it acts to determine the fate of common pancreatic precursor cells and/ or to regulate their propagation.
Journal ArticleDOI
Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similar to Pancreatic Islets
Nadya Lumelsky,Olivier Blondel,Olivier Blondel,Pascal Laeng,Iván Velasco,Rea Ravin,Ronald D.G. McKay +6 more
TL;DR: This work generated cells expressing insulin and other pancreatic endocrine hormones from mouse ES cells that self-assemble to form three-dimensional clusters similar in topology to normal pancreatic islets where pancreatic cell types are in close association with neurons.
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PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum
Martin F. Offield,T. L. Jetton,Patricia A. Labosky,Michael Ray,Roland Stein,Mark A. Magnuson,Brigid L.M. Hogan,Christopher V.E. Wright +7 more
TL;DR: The pdx-1/beta-galactosidase fusion allele is expressed in pancreatic and duodenal cells in the absence of functional PDX-1, with expression continuing into perinatal stages with similar boundaries and expression levels, and offers additional insight into the role of p dx-1 in the determination and differentiation of the posterior foregut.
Journal ArticleDOI
Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors.
TL;DR: The results provide direct evidence that NGN3+ cells are islet progenitors during embryogenesis and in adult mice, and suggest that lineages for exocrine, endocrine islet and duct progenitor are committed at mid-gestation.