RESUMO
A convenient technology to quantify three-dimensional (3D) morphological features would have widespread applications in biomedical research. Based on combined improvements in sample preparation, tomographic imaging and computational processing, we present a procedure for high-resolution 3D quantification of structures within intact adult mouse organs. Using the nonobese diabetic (NOD) mouse model, we demonstrate a correlation between total islet beta-cell volume and the onset of type-1 diabetes.
Assuntos
Diabetes Mellitus Tipo 1/diagnóstico , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Ilhotas Pancreáticas/patologia , Pâncreas/patologia , Tomografia/métodos , Animais , Diabetes Mellitus Tipo 1/fisiopatologia , Modelos Animais de Doenças , Progressão da Doença , Camundongos , Sensibilidade e EspecificidadeRESUMO
During early stages of pancreatic development, the mesenchyme that contributes to the spleen overlies the dorsal pancreatic endoderm. Here, we show that interactions between splenic mesenchyme and pancreas proceed via a highly orchestrated morphogenetic program. Disruption of morphogenesis, as occurs in the Bapx1(Nkx3.2)(-/-) embryo, results in transformation of these tissues into well-organized, ectopic gut-like structures. Bapx1 plays a crucial organizing role effecting position and separation of the spleen and pancreas to prevent this metaplastic transformation. Similar transformations occur in organ cultures employing wild-type pancreatic endoderm and spleen mesenchyme, revealing the developmental plasticity of the pancreas and that precise spatial and temporal control of tissue interactions are required for development of both organs.
Assuntos
Proteínas de Homeodomínio/fisiologia , Organogênese , Pâncreas/embriologia , Baço/embriologia , Fatores de Transcrição/fisiologia , Animais , Endoderma/metabolismo , Feminino , Proteínas Hedgehog , Proteínas de Homeodomínio/genética , Masculino , Mesoderma/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Modelos Animais , Mutação , Transativadores/metabolismo , Fatores de Transcrição/genéticaRESUMO
The A Disintegrin And Metalloprotease (ADAM) family of metalloproteases affects a variety of proteins with important roles in development and disease, including growth factors and adhesion molecules. We have analyzed the expression patterns of ADAMs 9, 10, and 17 during pancreas ontogeny. All ADAMs investigated were expressed in the pancreatic anlagen but invariably became restricted to divergent pancreatic compartments. ADAM9 and 17 became restricted to the insulin-producing beta-cells and all islet cells, respectively. During embryogenesis, ADAM10 was detected predominantly in acinar cells, but in the adult, it was localized to the cell surface membrane of both endocrine and exocrine cells. In addition to ADAM9, a potential prognostic factor for ductal cancers, we describe the expression of ADAM10 and ADAM17 in the pancreatic ductal epithelium. Altogether, the dynamic expression profile of the ADAM proteases described here may reflect a functional divergence of these as mediators of pancreas biology.