Friedrich Markus
Department of Biological Sciences, Wayne State University, 5047 Gullen Mall, Detroit, MI 48202, USA; Department of Anatomy and Cell Biology, Wayne State University, School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201,USA.
Dev Biol. 2017 Dec 1;432(1):192-200. doi: 10.1016/j.ydbio.2017.10.001. Epub 2017 Oct 6.
Pax6 transcription factors are essential upstream regulators in the developing anterior brain and peripheral visual system of most bilaterian animals. While a single homolog is in charge of these functions in vertebrates, two Pax6 genes are in Drosophila: eyeless (ey) and twin of eyeless (toy). At first glance, their co-existence seems sufficiently explained by their differential involvement in the specification of two types of insect visual organs: the lateral compound eyes (ey) and the dorsal ocelli (toy). Less straightforward to understand, however, is their genetic redundancy in promoting defined early and late growth phases of the precursor tissue to these organs: the eye-antennal imaginal disc. Drawing on comparative sequence, expression, and gene function evidence, I here conclude that this gene regulatory network module dates back to the dawn of arthropod evolution, securing the embryonic development of the ocular head segment. Thus, ey and toy constitute a paradigm to explore the organization and functional significance of longterm conserved genetic redundancy of duplicated genes. Indeed, as first steps in this direction, recent studies uncovered the shared use of binding sites in shared enhancers of target genes that are under redundant (string) and, strikingly, even subfunctionalized control by ey and toy (atonal). Equally significant, the evolutionarily recent and paralog-specific function of ey to repress the transcription of the antenna fate regulator Distal-less offers a functionally and phylogenetically well-defined opportunity to study the reconciliation of shared, partitioned, and newly acquired functions in a duplicated developmental gene pair.
Pax6转录因子是大多数两侧对称动物发育中的前脑和外周视觉系统中必不可少的上游调节因子。在脊椎动物中，单一的同源基因负责这些功能，而在果蝇中有两个Pax6基因：无眼基因（ey）和无眼双基因（toy）。乍一看，它们的共存似乎可以通过它们在两种昆虫视觉器官（侧复眼（ey）和背单眼（toy））的特化过程中不同的参与情况来充分解释。然而，较难理解的是，它们在促进这些器官的前体组织（眼触角成虫盘）特定的早期和晚期生长阶段方面存在基因冗余。基于比较序列、表达和基因功能证据，我在此得出结论，这个基因调控网络模块可追溯到节肢动物进化的开端，确保了头部眼节的胚胎发育。因此，ey和toy构成了一个探索重复基因长期保守的基因冗余的组织和功能意义的范例。事实上，作为朝着这个方向迈出的第一步，最近的研究发现，在受冗余（string）调控，甚至令人惊讶的是，受ey和toy（无调性基因）亚功能化控制的靶基因的共享增强子中存在共享的结合位点。同样重要的是，ey在进化上较新的、旁系同源基因特异性的功能是抑制触角命运调节因子Distal-less的转录，这为研究一对重复的发育基因中共享、分配和新获得的功能的协调提供了一个功能和系统发育上定义明确的机会。
