Unmasking Activation of the Zygotic Genome Using Chromosomal Deletions in the Drosophila Embryo

Abstract

During the maternal-to-zygotic transition, a developing embryo integrates post-transcriptional regulation of maternal mRNAs with transcriptional activation of its own genome. By combining chromosomal ablation in Drosophila with microarray analysis, we characterized the basis of this integration. We show that the expression profile for at least one third of zygotically active genes is coupled to the concomitant degradation of the corresponding maternal mRNAs. The embryo uses transcription and degradation to generate localized patterns of expression, and zygotic transcription to degrade distinct classes of maternal transcripts. Although degradation does not appear to involve a simple regulatory code, the activation of the zygotic genome starts from intronless genes sharing a common cis-element. This cis-element interacts with a single protein, the Bicoid stability factor, and acts as a potent enhancer capable of timing the activity of an exogenous transactivator. We propose that this regulatory mode links morphogen gradients with temporal regulation during the maternal-to-zygotic transition. Embryonic development is controlled by a complex interaction between maternal and zygotic activities. Maternal messenger RNAs and proteins are deposited in the unfertilized egg during oogenesis; after fertilization, the activation of the zygotic genome is accompanied by the degradation of a fraction of maternally supplied transcripts. This switch from maternal to zygotic control of development is characterized by a dramatic remodeling of gene expression, and represents a universal regulatory point during animal development. Because it is not usually possible to identify which genomes are contributing to these transcriptional changes, we have used chromosomal ablation to determine maternal versus zygotic contribution for each mRNA detectable on microarray in the Drosophila blastoderm. This has allowed us to distinguish transcriptional and post-transcriptional modes of regulation and to identify common cis-regulatory elements associated with different classes of transcripts. Our analysis revealed that although mRNA degradation does not involve a simple regulatory code, the activation of the zygotic genome is based on a simple mechanism, which links morphogen gradients with temporal regulation. It will be interesting to address whether similar mechanisms also operate in other animals.