Metabolic Regulation of Developmental Cell Cycles and Zygotic Transcription

The thirteen nuclear cleavages that give rise to the Drosophila blastoderm are some of the fastest known cell cycles [1]. Surprisingly, the fertilized egg is provided with at most one-third of the dNTPs needed to complete the thirteen rounds of DNA replication [2]. The rest must be synthesized by the embryo, concurrent with cleavage divisions. What is the reason for the limited supply of DNA building blocks? We propose that frugal control of dNTP synthesis contributes to the well-characterized deceleration of the cleavage cycles and is needed for robust accumulation of zygotic gene products. In support of this model, we demonstrate that when the levels of dNTPs are abnormally high, nuclear cleavages fail to sufficiently decelerate, the levels of zygotic transcription are dramatically reduced, and the embryo catastrophically fails early in gastrulation. Our work reveals a direct connection between metabolism, the cell cycle, and zygotic transcription. •Metabolic control of cell-cycle dynamics is shown•Decreasing dNTP levels slow down nuclear cleavages•Short nuclear cycles interfere with zygotic transcription Djabrayan et al. demonstrate a direct connection between dNTP metabolism, the cell cycle, and zygotic transcription at the midblastula transition in the Drosophila embryo. Dynamic restriction of dNTP levels is involved in the slowing down of nuclear divisions in the syncytial blastoderm, robust accumulation of zygotic gene products, and morphogenesis.