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Functional characterization of stap2b in zebrafish vascular development
Author(s) -
Wang YiShan,
Wu ChangYi
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.586.3
Subject(s) - morpholino , zebrafish , gene knockdown , microbiology and biotechnology , biology , notch signaling pathway , signal transducing adaptor protein , cell migration , cell growth , in situ hybridization , transcription factor , vascular smooth muscle , signal transduction , messenger rna , cell , gene , genetics , endocrinology , smooth muscle
Molecular mechanism of vascular formation is still not fully understood. We previously identified the transcription factors Islet2 (Isl2) and nr2f1b required for specification of the vein and ISV growth mediated by Notch pathway in zebrafish, and identify the potential downstream targets by performing the microarray experiments. In this study, we focus on the activation target signal‐transducing adaptor protein 2b (stap2b) and confirmed this gene expressed in vessels during early development indicating stap2b function in vascular development. stap2 is identified as an adaptor protein that has been showed functions in a variety of cellular signal pathways in immune system, however, there is no description of stap2b functioning in vascular development so far. Our in‐situ hybridization results showed stap2b mRNA expressed in developing vessels, suggesting its roles in vasculization. Knockdown of stap2b by morpholino injection causes vascular defects, suggesting the role of stap2b in controlling ISV and CVP growth. AO staining and TUNEL assay showed that vascular defects do not caused by cell death, but due to the impairment of migration and/or proliferation by examining ISV integrity and ISV cell numbers in Tg(kdrl:mCherry; fli:neGFP y7 ) fish. We also found a decreased expression of flk , stabilin, enphrinb2, and flt4 in stap2b morphants. Moreover, overexpression of stap2b enhanced the growth of ISV and promotes endothelial cell migration and/or proliferation. These data suggest that stap2b is necessary and sufficient to promote vascular development. We further examine the interaction between stap2b and Notch signals, we showed stap2b is regulated by Notch signals to control ISV growth. In addition, stap2b may interact with BMP signaling to function in CVP formation. Together, we conclude that our microarray results identify stap2b acting downstream of isl2/ nr2f1b pathway. We also showed that stap2b plays an important role for vascular development in zebrafish.