Li Ru-Fang, Wang Yi-Shan, Lu Fu-I, Huang Yi-Shan, Chiu Chien-Chih, Tai Ming-Hong, Wu Chang-Yi
Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan.
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University, Kaohsiung 804, Taiwan.
Biomedicines. 2022 May 27;10(6):1261. doi: 10.3390/biomedicines10061261.
The genetic regulation of vascular development is not elucidated completely. We previously characterized the transcription factors Islet2 (Isl2) and Nr2f1b as being critical for vascular growth. In this study, we further performed combinatorial microarrays to identify genes that are potentially regulated by these factors. We verified the changed expression of several targets in morphants. Those genes expressed in vessels during embryogenesis suggested their functions in vascular development. We selectively assayed a potential target ). Follistatin is known to inhibit BMP, and BMP signaling has been shown to be important for angiogenesis. However, the 's role in vascular development has not been well studied. Here, we showed the vascular defects in ISV growth and CVP patterning while overexpressing in the embryo, which mimics the phenotype of morphants. The vascular abnormalities are likely caused by defects in migration and proliferation. We further observed the altered expression of vessel markers consistent with the vascular defects in embryos. We showed that the knockdown of can rescue the vascular defects in fish, suggesting the functional specificity of . Moreover, the decreased expression of rescues abnormal vessel growth in and morphants, indicating that functions downstream of /. Lastly, we showed that Isl2/Nr2f1b control vascular development, via Fsta-BMP signaling in part. Collectively, our microarray data identify many interesting genes regulated by , which likely function in the vasculature. Our research provides useful information on the genetic control of vascular development.
血管发育的基因调控尚未完全阐明。我们之前将转录因子胰岛2（Isl2）和Nr2f1b鉴定为对血管生长至关重要的因子。在本研究中，我们进一步进行了组合微阵列分析，以鉴定可能受这些因子调控的基因。我们验证了几种靶标在形态突变体中的表达变化。那些在胚胎发育过程中在血管中表达的基因表明它们在血管发育中的功能。我们选择性地检测了一个潜在靶标。已知卵泡抑素可抑制骨形态发生蛋白（BMP），并且BMP信号已被证明对血管生成很重要。然而，其在血管发育中的作用尚未得到充分研究。在这里，我们展示了在胚胎中过表达时，在节间血管（ISV）生长和尾静脉丛（CVP）模式形成方面的血管缺陷，这模拟了形态突变体的表型。血管异常可能是由迁移和增殖缺陷引起的。我们进一步观察到与胚胎中的血管缺陷一致的血管标记物表达改变。我们表明，敲低可以挽救鱼中的血管缺陷，表明的功能特异性。此外，表达的降低挽救了和形态突变体中的异常血管生长，表明在/的下游起作用。最后，我们表明Isl2/Nr2f1b部分通过Fsta-BMP信号传导控制血管发育。总体而言，我们的微阵列数据鉴定了许多受调控的有趣基因，它们可能在脉管系统中发挥作用。我们的研究为血管发育的基因控制提供了有用的信息。
