NAD(P)H dependent steroid dehydrogenase-like (nsdhl) involved in cholesterol biosynthesis is critical for vascular development in zebrafish

• Main Authors: Shuo-Rong Liang, 梁碩容
• Other Authors: Chang-Yi Wu
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/6788yq

碩士 === 國立中山大學 === 生物科學系研究所 === 107 === Genetic conrol of vascular development and patterning in vertebrates is not fully understood. We used zebrafish as a model organism to identify transcription factors Islet2 (Isl2) and Nr2f1b required for the growth of intersegmental vessels (ISV) and caudal vein plexus (CVP). We further identify NAD(P)H steroid dehydrogenase-like (Nsdhl) gene is positively regulated by Isl2 /Nr2f1b. Nsdhl is a dehydrogenase that participates in sterol production in cholesterol biosynthesis. Excess cellular cholesterol often leads to abnormal proliferation and migration. In addition, recent study showed cholesterol efflux related to angiogenesis control. Here, we show Nsdhl is highly conserved in all species. Nsdhl mRNA is expressed in vessels, suggesting its roles in vascular development. Knockdown of Nsdhl expression by Morpholino (MO) disrupts the growth of ISV and CVP, suggesting the role of Nsdhl in controlling ISV and CVP growth. Consist with the defects in vascular development, we examined the expression of vascular markers flk1, mrc1, stabilin, flt4 and ephrinb2 and we found the remodeling the expression of vascular markers in Nsdhl MO. To address whether the cell death contributes to the ISV and CVP defects in Nsdhl MO, we performed AO staining and TUNEL assay. The data showed that vascular defects do not caused by cell death, but likely due to the impairment of proliferation and migration. We also revealed the relationship between Nsdhl and Notch/VEGF signals. In addition, Nsdhl may interact with BMP signaling to function in CVP formation. Together, we showed that Nsdhl plays important role for vascular development in zebrafish.