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1.
Dev Biol ; 420(1): 67-78, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27789228

RESUMO

The vertebrate pancreas is comprised of a highly branched tubular epithelium, which is intimately associated with an extensive and specialized vasculature. While we know a great deal about basic vascular anatomy of the adult pancreas, as well as islet capillaries, surprisingly little is known about the ontogeny of its blood vessels. Here, we analyze development of the pancreatic vasculature in the mouse embryo. We show that pancreatic epithelial branches intercalate with the fine capillary plexus of the surrounding pancreatic mesenchyme. Endothelial cells (ECs) within this mesenchyme are heterogeneous from the onset of organogenesis. Pancreatic arteries take shape before veins, in a manner analogous to early embryonic vessels. The main central artery forms during mid-gestation, as a result of vessel coalescence and remodeling of a vascular plexus. In addition, we show that vessels in the forming pancreas display a predictable architecture that is dependent on VEGF signaling. Over-expression of VEGF disrupts vascular patterning and arteriovenous differentiation within the developing pancreas. This study constitutes a first-time in-depth cellular and molecular characterization of pancreatic blood vessels, as they coordinately grow along with the pancreatic epithelium.


Assuntos
Vasos Sanguíneos/embriologia , Neovascularização Fisiológica , Pâncreas/irrigação sanguínea , Pâncreas/embriologia , Vertebrados/embriologia , Animais , Artérias/embriologia , Padronização Corporal , Capilares/embriologia , Epitélio/irrigação sanguínea , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Imageamento Tridimensional , Camundongos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Remodelação Vascular , Veias/embriologia
2.
Dev Biol ; 406(2): 222-34, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26321050

RESUMO

Wnt signaling is essential to many events during organogenesis, including the development of the mammalian lung. The Wnt family member Wnt4 has been shown to be required for the development of kidney, gonads, thymus, mammary and pituitary glands. Here, we show that Wnt4 is critical for proper morphogenesis and growth of the respiratory system. Using in situ hybridization in mouse embryos, we identify a previously uncharacterized site of Wnt4 expression in the anterior trunk mesoderm. This expression domain initiates as early as E8.25 in the mesoderm abutting the tracheoesophageal endoderm, between the fusing dorsal aortae and the heart. Analysis of Wnt4(-/-) embryos reveals severe lung hypoplasia and tracheal abnormalities; however, aortic fusion and esophageal development are unaffected. We find decreased cell proliferation in Wnt4(-/-) lung buds, particularly in tip domains. In addition, we observe reduction of the important lung growth factors Fgf9, Fgf10, Sox9 and Wnt2 in the lung bud during early stages of organogenesis, as well as decreased tracheal expression of the progenitor factor Sox9. Together, these data reveal a previously unknown role for the secreted protein Wnt4 in respiratory system development.


Assuntos
Proliferação de Células/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Pulmão/embriologia , Via de Sinalização Wnt/fisiologia , Proteína Wnt4/metabolismo , Animais , Primers do DNA/genética , Fator 10 de Crescimento de Fibroblastos/metabolismo , Fator 9 de Crescimento de Fibroblastos/metabolismo , Imuno-Histoquímica , Hibridização In Situ , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Knockout , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição SOX9/metabolismo , Proteína Wnt2/metabolismo , Proteína Wnt4/genética
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