Zebrafish Zic genes mediate developmental signaling

Abstract

The introduction of genomics into the field of developmental biology led to a vast expansion of knowledge about developmental genes and signaling mechanisms they are involved in. Unlike mammals, the zebrafish features seven Zic genes. This provides an interesting insight into Zic gene evolution. In addition, an unprecedented bioimaging capability of semitransparent zebrafish embryos turns to be a crucial factor in medium- to large-scale analysis of the activity of potential regulatory elements. The Zic family of zinc finger proteins plays an important, relatively well-established, role in the regulation of stem cells and neural development and, in particular, during neural fate commitment and determination. At the same time, some Zic genes are expressed in mesodermal lineages, and their deficiency causes a number of developmental defects in axis formation, establishing body symmetry and cardiac morphogenesis. In stem cells, Zic genes are required to maintain pluripotency by binding to the proximal promoters of pluripotency genes (Oct4, Nanog, Sox2, etc.). During embryogenesis, the dynamic nature of Zic transcriptional regulation is manifested by the interaction of these factors with distal enhancers and other regulatory elements associated with the control of gene transcription and, in particular, with the Nodal and Wnt signaling pathways that play a role in establishing basic organization of the vertebrate body. Zic transcription factors may regulate development through acting alone as well as in combination with other transcription factors. This is achieved due to Zic binding to sites adjacent to the binding sites of other transcription factors, including Gli. This probably leads to the formation of multi-transcription factor complexes associated with enhancers.