Summary
Upon fertilization, maternal factors direct development and trigger zygotic genome activation (ZGA) at the maternal-to-zygotic transition (MZT). In zebrafish, ZGA is required for gastrulation and clearance of maternal mRNAs, which is in part regulated by the conserved microRNA miR-430. However, the factors that activate the zygotic program in vertebrates are unknown. Here, we show that Nanog, Pou5f1 and SoxB1 regulate zygotic gene activation in zebrafish. We identified several hundred genes directly activated by maternal factors, constituting the first wave of zygotic transcription. Ribosome profiling revealed that nanog, sox19b and pou5f1 are the most highly translated transcription factors pre-MZT. Combined loss of these factors resulted in developmental arrest prior to gastrulation and a failure to activate >75% of zygotic genes, including miR-430. Our results demonstrate that maternal Nanog, Pou5f1 and SoxB1 are required to initiate the zygotic developmental program and induce clearance of the maternal program by activating miR-430 expression.
Embryogenesis depends on a highly coordinated cascade of genetically encoded events. In animals, maternal factors contributed by the egg cytoplasm initially control development, while the zygotic nuclear genome is quiescent. Subsequently, the genome is activated, embryonic gene products are mobilized and maternal factors are cleared. This transfer of developmental control is called the maternal-to-zygotic transition (MZT). In this review, we discuss recent advances toward understanding the scope, timing and mechanisms that underlie zygotic genome activation at the MZT in animals. We describe high-throughput techniques to measure the embryonic transcriptome and explore how regulation of the cell cycle, chromatin and transcription factors together elicits specific patterns of embryonic gene expression. Finally, we discuss the interplay between zygotic transcription and maternal clearance, and show how these two activities combine to reprogram two terminally differentiated gametes into a totipotent embryo.
As the range and duration of human ventures into space increase, it becomes imperative that we understand the effects of the cosmic environment on astronaut health. Molecular technologies now widely used in research and medicine will need to become available in space to ensure appropriate care of astronauts. The polymerase chain reaction (PCR) is the gold standard for DNA analysis, yet its potential for use on-orbit remains under-explored. We describe DNA amplification aboard the International Space Station (ISS) through the use of a miniaturized miniPCR system. Target sequences in plasmid, zebrafish genomic DNA, and bisulfite-treated DNA were successfully amplified under a variety of conditions. Methylation-specific primers differentially amplified bisulfite-treated samples as would be expected under standard laboratory conditions. Our findings establish proof of concept for targeted detection of DNA sequences during spaceflight and lay a foundation for future uses ranging from environmental monitoring to on-orbit diagnostics.
Neuronal circuits damaged or lost after injury can be regenerated in some adult organisms, but the mechanisms enabling this process are largely unknown. We used the planarian Schmidtea mediterranea to study visual system regeneration after injury. We identify a rare population of muscle cells tightly associated with photoreceptor axons at stereotyped positions in both uninjured and regenerating animals. Together with a neuronal population, these cells promote de novo assembly of the visual system in diverse injury and eye transplantation contexts. These muscle guidepost-like cells are specified independently of eyes, and their position is defined by an extrinsic array of positional information cues. These findings provide a mechanism, involving adult formation of guidepost-like cells typically observed in embryos, for axon pattern restoration in regeneration.
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