(Journal Article): Transcribing pancreas.
Edlund H (Department of Microbiology, University of Umea, Sweden.,
helena.edlund@micro.umu.se
)
IN:
Diabetes
1998; 47(12):1817-1823
Impact Factor(s) of Diabetes: 8.848 (2004), 8.298 (2003), 8.256 (2002), 7.7 (2001)
Fulltext: PDF
ABSTRACT: For approximately 30-35 years, our insight into some of the fundamental aspects of pancreas development has been based mainly on two independent studies performed in the 1960s by Golosow and Grobstein and Wessells and Cohen. By performing classical embryological experiments, these two reports described the morphogenesis of the pancreas and the epitheliomesenchymal interactions that are required for proper pancreas development. In the 1970s, the groups of LeDourain and associates and Rutter and associates showed, importantly, that despite their similarities with neurons, the pancreatic endocrine cells, like the exocrine and ductual cells, were of an endodermal origin. Then during the 1980s, studies pioneered by Rutter, but also performed by many other groups, were focused on the transcriptional regulation of endocrine and exocrine genes. This eventually lead to the cloning of various transcription factors. By using a genetic approach to study the function of these transcription factors, new insights into pancreas development have now emerged that, on a molecular level, are beginning to explain some of the earlier observations. This review discusses our current knowledge of the mechanisms by which the various pancreatic cell types are generated.
TYPE OF PUBLICATION: Review
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(Journal Article): Expression of neurogenin3 reveals an islet cell precursor population in the pancreas.
Schwitzgebel VM, Scheel DW, Conners JR, Kalamaras J, Lee JE, Anderson DJ, Sussel L, Johnson JD, German MS (Hormone Research Institute, Department of Pediatrics, and Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.)
IN:
Development
2000; 127(16):3533-3542
Impact Factor(s) of Development: 7.149 (2004), 7.663 (2003), 8.624 (2001)
Fulltext: PDF
ABSTRACT: Differentiation of early gut endoderm cells into the endocrine cells forming the pancreatic islets of Langerhans depends on a cascade of gene activation events controlled by transcription factors including the basic helix-loop-helix (bHLH) proteins. To delineate this cascade, we began by establishing the position of neurogenin3, a bHLH factor found in the pancreas during fetal development. We detect neurogenin3 immunoreactivity transiently in scattered ductal cells in the fetal mouse pancreas, peaking at embryonic day 15.5. Although not detected in cells expressing islet hormones or the islet transcription factors Isl1, Brn4, Pax6 or PDX1, neurogenin3 is detected along with early islet differentiation factors Nkx6.1 and Nkx2.2, establishing that it is expressed in immature cells in the islet lineage. Analysis of transcription factor-deficient mice demonstrates that neurogenin3 expression is not dependent on neuroD1/BETA2, Mash1, Nkx2.2, Nkx6.1, or Pax6. Furthermore, early expression of neurogenin3 under control of the Pdx1 promoter is alone sufficient to drive early and ectopic differentiation of islet cells, a capability shared by the pancreatic bHLH factor, neuroD1/BETA2, but not by the muscle bHLH factor, MyoD. However, the islet cells produced in these transgenic experiments are overwhelmingly (alpha) cells, suggesting that factors other than the bHLH factors are required to deviate from a default * cell fate. These data support a model in which neurogenin3 acts upstream of other islet differentiation factors, initiating the differentiation of endocrine cells, but switching off prior to final differentiation. The ability to uniquely identify islet cell precursors by neurogenin3 expression allows us to determine the position of other islet transcription factors in the differentiation cascade and to propose a map for the islet cell differentiation pathway.
TYPE OF PUBLICATION: Original article
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(Journal Article): Control of early development of the pancreas in rodents and humans: implications of signals from the mesenchyme.
Scharfmann R (INSERM U457 Hospital R. Debre, Paris.)
IN:
Diabetologia
2000; 43(9):1083-1092
Impact Factor(s) of Diabetologia: 5.583 (2004), 5.689 (2003), 5.136 (2002), 6.299 (2001)
ABSTRACT: During the last few years, progress has been made in the control of pancreatic development. Many transcription factors have been described in the pancreas and a genetic approach has been used to define their role in pancreatic development. Pancreatic development depends on mesodermic signals, with the initial steps controlled by signals from the notochord that is in close contact with the dorsal endoderm of the gut fated to become pancreas. Later signals from the mesenchyme that surrounds the embryonic pancreatic epithelium regulate the proliferation of immature pancreatic epithelial cells and their differentiation into endocrine or exocrine tissue. This review discusses recent data on the role the signals from the mesenchyme have in the development of the pancreas in rodents and humans.
TYPE OF PUBLICATION: Review
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(Journal Article): Pancreas: how to get there from the gut?
Edlund H (Department of Microbiology, University of Umea, Umea, SE-901 87, Sweden.,
Helena.Edlund@micro.umu.se.
)
IN:
Curr Op Cell Biol
1999; 11(6):663-668
ABSTRACT: All pancreatic cell types derive from the same endodermal dorsal and ventral anlage that grow together to form the definitive pancreas. A number of distinct transcription factors operating at various levels of pancreatic development, and in different cell-types, have been identified and their functions have, in many cases, been genetically analyzed. This knowledge has given us useful information both on pancreas development and on various pancreatic disorders, such as diabetes. However, the extrinsic factors that ultimately control the process leading from the primitive gut endoderm to a fully developed, functional pancreas needs now to be identified. With such information, the prospect of using pancreatic stem and/or progenitor cells as a therapeutic approach towards curing diabetic disorders will be within reach.
TYPE OF PUBLICATION: Review
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