School of Medicine, Deakin University, Geelong, VIC 3216, Australia.
Institute of Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC 3216, Australia.
Int J Mol Sci. 2022 Sep 3;23(17):10098. doi: 10.3390/ijms231710098.
Members of the FOS protein family regulate gene expression responses to a multitude of extracellular signals and are dysregulated in several pathological states. Whilst mouse genetic models have provided key insights into the tissue-specific functions of these proteins in vivo, little is known about their roles during early vertebrate embryonic development. This study examined the potential of using zebrafish as a model for such studies and, more broadly, for investigating the mechanisms regulating the functions of Fos proteins in vivo. Through phylogenetic and sequence analysis, we identified six zebrafish orthologues, and , which show high conservation in key regulatory domains and post-translational modification sites compared to their equivalent human proteins. During embryogenesis, zebrafish genes exhibit both overlapping and distinct spatiotemporal patterns of expression in specific cell types and tissues. Most genes are also expressed in a variety of adult zebrafish tissues. As in humans, we also found that expression of zebrafish orthologs is induced by oncogenic BRAF-ERK signalling in zebrafish melanomas. These findings suggest that zebrafish represent an alternate model to mice for investigating the regulation and functions of Fos proteins in vertebrate embryonic and adult tissues, and cancer.
FOS 蛋白家族的成员调节基因表达对多种细胞外信号的反应，并且在几种病理状态下失调。虽然小鼠遗传模型为这些蛋白质在体内的组织特异性功能提供了关键见解，但对它们在早期脊椎动物胚胎发育中的作用知之甚少。本研究探讨了使用斑马鱼作为此类研究模型的可能性，更广泛地说，是为了研究调节 Fos 蛋白在体内功能的机制。通过系统发育和序列分析，我们鉴定了六种斑马鱼 同源物， 和 ，与相应的人类蛋白质相比，它们在关键调节域和翻译后修饰位点具有高度保守性。在胚胎发生过程中，斑马鱼 基因在特定细胞类型和组织中表现出重叠和独特的时空表达模式。大多数 基因也在各种成年斑马鱼组织中表达。与人类一样，我们还发现斑马鱼 同源物的表达也被斑马鱼黑色素瘤中的致癌 BRAF-ERK 信号诱导。这些发现表明，斑马鱼代表了一种替代的小鼠模型，可用于研究 Fos 蛋白在脊椎动物胚胎和成年组织以及癌症中的调节和功能。
