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Development ; 145(15)2018 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-29986868

RESUMO

The synchronized differentiation of neuronal and vascular tissues is crucial for normal organ development and function, although there is limited information about the mechanisms regulating the coordinated development of these tissues. The choroid vasculature of the eye serves as the main blood supply to the metabolically active photoreceptors, and develops together with the retinal pigmented epithelium (RPE). Here, we describe a novel regulatory relationship between the RPE transcription factors Pax6 and Sox9 that controls the timing of RPE differentiation and the adjacent choroid maturation. We used a novel machine learning algorithm tool to analyze high resolution imaging of the choroid in Pax6 and Sox9 conditional mutant mice. Additional unbiased transcriptomic analyses in mutant mice and RPE cells generated from human embryonic stem cells, as well as chromatin immunoprecipitation and high-throughput analyses, revealed secreted factors that are regulated by Pax6 and Sox9. These factors might be involved in choroid development and in the pathogenesis of the common blinding disease: age-related macular degeneration (AMD).


Assuntos
Diferenciação Celular , Corioide/irrigação sanguínea , Corioide/metabolismo , Neovascularização Fisiológica , Fator de Transcrição PAX6/metabolismo , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/metabolismo , Fatores de Transcrição SOX9/metabolismo , Algoritmos , Animais , Sequência de Bases , Regulação da Expressão Gênica no Desenvolvimento , Aprendizado de Máquina , Degeneração Macular/genética , Degeneração Macular/patologia , Camundongos Endogâmicos C57BL , Modelos Biológicos , Fatores de Transcrição SOX9/genética , Fatores de Tempo , Regulação para Cima/genética
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