Redundant roles of Sox17 and Sox18 in early cardiovascular development of mouse embryos

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Abstract

Sox7, -17 and -18 constitute the Sox subgroup F (SoxF) of HMG box transcription factor genes, which all are co-expressed in developing vascular endothelial cells in mice. Here we characterized cardiovascular phenotypes of Sox17/Sox18-double and Sox17-single null embryos during early-somite stages. Whole-mount PECAM staining demonstrated the aberrant heart looping, enlarged cardinal vein and mild defects in anterior dorsal aorta formation in Sox17 single-null embryos. The Sox17/Sox18 double-null embryos showed more severe defects in formation of anterior dorsal aorta and head/cervical microvasculature, and in some cases, aberrant differentiation of endocardial cells and defective fusion of the endocardial tube. However, the posterior dorsal aorta and allantoic microvasculature was properly formed in all of the Sox17/Sox18 double-null embryos. The anomalies in both anterior dorsal aorta and head/cervical vasculature corresponded with the weak Sox7 expression sites. This suggests the region-specific redundant activities of three SoxF members along the anteroposterior axis of embryonic vascular network.

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Materials and methods

Animals and genotyping. Sox17/Sox18 double mutant animals (the mixed background of C57BL/6, 129sv and CD1 strains) were generated by interbreeding Sox17+/−-Sox18+/− mice obtained by crossing Sox17+/−[16] and Sox18−/−[13] mice. The embryos of Sox17−/−/Sox18−/− and Sox17−/−/Sox18+/+ mutants (8.25–9.0 dpc) were obtained from the pregnant Sox17+/−/Sox18+/− females by crossing with Sox17+/−/Sox18−/− or Sox17+/−/Sox18+/+ males. Genomic DNA from tail tips or yolk sac was isolated using a Wizard genomic

Aberrant heart looping and enlarged cardinal veins in Sox17-null embryos at early-somite stages

Our previous study demonstrated that Sox17-null embryos display defective formation of the definitive endoderm and subsequently show no axis turning with poor posterior trunk development, resulting in embryonic lethality before 10.5 dpc [16]. In order to clarify the influence of the Sox17-single null mutation on early cardiovascular development, we first examined the phenotype of Sox17−/−(/Sox18+/+) embryos as compared with the wildtype embryos at early-somite stages (8.0–8.75 dpc), before the

Acknowledgments

The authors thank Ms. I. Yagihashi for technical and secretarial support. This work was supported by financial grants from the Ministry of Education, Science, Sports and Culture of Japan to Y. Kanai (B-17380175, B-19380168, PA-16086203) and M. Kanai-Azuma (PA-16027247). This work was also supported by financial grants from National Health and Medical Research Council (NHMRC) and National Heart Foundation of Australia to P. Koopman, and from the Eccles Program in Human Molecular Biology and

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      For example, Corada et al. demonstrated that Sox17 deletion in a C57Bl/6 J mouse embryo resulted in a fusion of the dorsal aorta and cardinal vein inferring that Sox17 is crucial for arterial specification [19]. In contrast, another Sox17 knockout study of a mouse embryo (mixed background of C57BL/6, 129sv and CD1 strains) only led to mild malformations of the anterior dorsal aorta as another SoxF member, Sox18, compensated for the deficiency [25]. Similar observations of partial effects have been observed by other groups, and it is thought that these particular discrepancies are due to differences in genetic background and phenotype variation [26–28].

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    These authors contributed equally to this study.

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