Regulatory principles governing the maternal-to-zygotic transition: insights from Drosophila melanogaster

Abstract

The onset of metazoan development requires that two terminally differentiated germ cells, a sperm and an oocyte, become reprogrammed to the totipotent embryo, which can subsequently give rise to all the cell types of the adult organism. In nearly all animals, maternal gene products regulate the initial events of embryogenesis while the zygotic genome remains transcriptionally silent. Developmental control is then passed from mother to zygote through a process known as the maternal-to-zygotic transition (MZT). The MZT comprises an intimately connected set of molecular events that mediate degradation of maternally deposited mRNAs and transcriptional activation of the zygotic genome. This essential developmental transition is conserved among metazoans but is perhaps best understood in the fruit fly, Drosophila melanogaster. In this article, we will review our understanding of the events that drive the MZT in Drosophila embryos and highlight parallel mechanisms driving this transition in other animals.

The Lid/KDM5 histone demethylase complex activates a critical effector of the oocyte-to-zygote transition

“…Generally, the spermatozoon delivers its compact nucleus within the egg cytoplasm, along with a pair of centrioles, while the egg provides one haploid meiotic product and all resources to sustain zygote formation [1]. In some species, this maternal control extends to early embryo development, as in Drosophila melanogaster, where the initial amplification of embryo cleavage nuclei occurs without significant zygotic transcription [2]. The developmental potential of the egg is thus initially dependent on the establishment of a highly complex transcriptional program in female germ cells.…”

Odd-paired is a late-acting pioneer factor coordinating with Zelda to broadly regulate gene expression in early embryos

“…It has been hypothesized that the initiation of genes sensitive to N/C ratio is sensitive to repression, which is diluted out with increasing N/C ratio possibly to concentrate an activator (e.g. Hamm and Harrison, 2018) . We propose that genes of different timing classes may be preferentially regulated by different pioneer factors (Opa versus Zld, for example).…”

“…During the maternal-to-zygotic transition (MZT), maternal products are cleared and zygotic genome activation occurs (rev. in Hamm and Harrison, 2018;Vastenhouw et al, 2019) . In Drosophila embryos, the first 13 mitotic divisions involve rapid nuclear cycles (nc), that include only a short DNA replication S phase and no G2 phase, and the nuclei are not enclosed in separate membrane compartments but instead present in a joint cytoplasm (Foe and Alberts, 1983) .…”

“…The exact molecular mechanism that supports widespread activation of zygotic gene expression is not known, but several regulatory mechanisms have been proposed. One model suggests that a decrease in histone levels occurs over time that provides an opportunity for the pioneer factors that herald zygotic gene expression to successfully compete for DNA, in order to access and activate transcription (Hamm and Harrison, 2018;Shindo and Amodeo, 2019) . For example, Zld is a pivotal activator of the MZT as it increases accessibility of chromatin at enhancers, to facilitate binding of other transcriptional activators to these DNA sequences and thereby allow initiation of zygotic gene expression (Harrison et al, 2011;Liang et al, 2008;Nien et al, 2011) .…”

Zelda, le maestro du réveil du génome zygotique

“…Environ deux heures après la fécondation, le génome zygotique s'active transcriptionnellement et le syncytium se sépare en cellules individuelles (cellularisation) comportant chacune un seul noyau ( Figure 1A). Le réveil transcriptionnel du génome zygotique nécessite des facteurs de transcription spécifiques, dont la protéine Zelda, qui joue un rôle essentiel dans ce processus [2]. Zelda possède plusieurs caractéristiques des facteurs de transcription dits « pionniers » : 1) sa liaison aux éléments cis-régulateurs avant l'activation des gènes, établissant une pré-compétence pour l'adoption de certains destins cellulaires, et 2) sa capacité à ouvrir la chromatine pour faciliter la liaison de facteurs de transcription classiques.…”