期刊
DEVELOPMENTAL BIOLOGY
卷 387, 期 1, 页码 109-120出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2013.11.018
关键词
Sox17; Lung; Endothelial; Vascular morphogenesis; Dermo1-Cre
资金
- NIH Lung Regeneration and Repair Consortium (LRRC) [HL090156, HL110964]
- Medical Research Council Clinician [G0802804]
- Medical Research Council [G0802804] Funding Source: researchfish
- MRC [G0802804] Funding Source: UKRI
The SRY-box containing transcription factor Sox17 is required for endoderm formation and vascular morphogenesis during embryonic development. In the lung, Sox17 is expressed in mesenchymal progenitors of the embryonic pulmonary vasculature and is restricted to vascular endothelial cells in the mature lung. Conditional deletion of Sox17 in splanchnic mesenchyme-derivatives using Dermol-Cre resulted in substantial loss of Sox17 from developing pulmonary vascular endothelial cells and caused pulmonary vascular abnormalities before birth, including pulmonary vein varices, enlarged arteries, and decreased perfusion of the microvasculature. While survival of Dermol-Cre;Sox17 Delta/Delta mice (herein termed Sox17 Delta/Delta) was unaffected at E18.5, most Sox17 Delta/Delta mice died by 3 weeks of age. After birth, the density of the pulmonary microvasculature was decreased in association with alveolar simplification, biventricular cardiac hypertrophy, and valvular regurgitation. The severity of the postnatal cardiac phenotype was correlated with the severity of pulmonary vasculature abnormalities. Sox17 is required for normal formation of the pulmonary vasculature and postnatal cardiovascular homeostasis. (C) 2014 Elsevier Inc. All rights reserved.
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