Expression of neurogenin3 reveals an islet cell precursor population in the pancreas

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 α cells, suggesting that factors other than the bHLH factors are required to deviate from a default α 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

Diferentes parâmetros patométricos para avaliação da ferrugem asiática em linhagens transgênicas de soja.

A ferrugem asiática está disseminada em todas regiões produtoras de soja do Brasil. Os sintomas iniciais da doença são pequenas pústulas foliares, de cor castanha a marromescura, podem ser classificadas como do tipo castanho clara com muitos soros urediniais e abundante esporulação (TAN) ou castanho avermelhada com poucos soros urediniais e com pouca ou nenhuma esporulação (RB).Observou-se diferença estatística entre as médias de severidade e de desfolha causadas pela ferrugem asiática, nos diferentes tratamentos com fungicidas nos três estratos avaliados. Tratamentos com apenas uma pulverização não apresentaram diferenças significativas em relação aos tratamentos com três pulverizações. Houve diferença estatística entre as médias de número de esporos contados em hemocitômetro, assim como as médias de notas de coloração de ustulas e de esporulação nas pústulas. Nestas três avaliações os resultados dos tratamentos que receberam uma pulverização diferiram estatisticamente dos que receberam três pulverizações. Ao correlacionar cor de pústula e esporulação visual com os demais parâmetros analisados, observou-se correlações significativas com os parâmetros de desfolha, contudo o parâmetro número de esporos contados em hemocitômetro não se correlacionou com nenhum outro parâmetro e o parâmetro severidade apresentou correlação negativa Apesar da severidade apresentar correlação negativa com a maioria dos demais parâmetros, esta apresenta correlação positiva com a avaliação de desfolha. A avaliação de desfolha também se apresentou correlações significativas porém negativas com a cor das pústulas com a esporulação visual das mesmas

Regulation of Neurod1 Contributes to the Lineage Potential of Neurogenin3+ Endocrine Precursor Cells in the Pancreas

During pancreatic development, transcription factor cascades gradually commit precursor populations to the different endocrine cell fate pathways. Although mutational analyses have defined the functions of many individual pancreatic transcription factors, the integrative transcription factor networks required to regulate lineage specification, as well as their sites of action, are poorly understood. In this study, we investigated where and how the transcription factors Nkx2.2 and Neurod1 genetically interact to differentially regulate endocrine cell specification. In an Nkx2.2 null background, we conditionally deleted Neurod1 in the Pdx1+ pancreatic progenitor cells, the Neurog3+ endocrine progenitor cells, or the glucagon+ alpha cells. These studies determined that, in the absence of Nkx2.2 activity, removal of Neurod1 from the Pdx1+ or Neurog3+ progenitor populations is sufficient to reestablish the specification of the PP and epsilon cell lineages. Alternatively, in the absence of Nkx2.2, removal of Neurod1 from the Pdx1+ pancreatic progenitor population, but not the Neurog3+ endocrine progenitor cells, restores alpha cell specification. Subsequent in vitro reporter assays demonstrated that Nkx2.2 represses Neurod1 in alpha cells. Based on these findings, we conclude that, although Nkx2.2 and Neurod1 are both necessary to promote beta cell differentiation, Nkx2.2 must repress Neurod1 in a Pdx1+ pancreatic progenitor population to appropriately commit a subset of Neurog3+ endocrine progenitor cells to the alpha cell lineage. These results are consistent with the proposed idea that Neurog3+ endocrine progenitor cells represent a heterogeneous population of unipotent cells, each restricted to a particular endocrine lineage

News of an epidemic : exploring the discourse of 'deviance' in the construction of AIDS

In reporting on the AIDS epidemic, Canadian media have shied away from dealing forthrightly with gay men