Nareg Djabrayan (Shvartsman lab): Metabolic Tuning of Cell Cycle in the Early Drosophila Embryo
The 13 nuclear cleavages that give rise to the Drosophila blastoderm are some of the fastest known developmental cell cycles. Surprisingly, the fertilized egg contains at most 1/3 of the dNTPs needed to complete all 13 rounds of DNA replication. The rest must be synthesized concurrently with nuclear cleavages. What is the reason for such a restricted supply of DNA building blocks in early embryogenesis? We propose that frugal control of dNTP synthesis contributes to the well-characterized deceleration of nuclear cleavages and ensures robust accumulation of zygotic transcript. Indeed, we demonstrate that in the presence of abnormally high dNTP concentrations nuclear cleavages fail to sufficiently decelerate, the levels of zygotic transcription are dramatically reduced, and the embryo fails early in gastrulation. Our work reveals a direct connection between metabolism, cell cycle, and gene expression during the first steps of embryonic development.
Cholsoon Jang (Rabinowitz lab): How different organs work together to maintain metabolic homeostasis
Organs continually exchange metabolites via circulation, but systems-level analysis of this shuttling process is lacking. Here we compared, in fasted pigs, the concentration of 280 metabolites between the arterial blood and draining veins of 11 organs. Greater than 90% of metabolites showed significant arterial-venous differences across at least one organ. Consistent with their gluconeogenic function, both the liver and kidneys released glucose. Unexpectedly, both also released amino acids. The glucose and amino acids were primarily consumed by the gastrointestinal system, which showed the most active protein synthesis. Both the kidneys and liver also showed unanticipated fuel preferences: The kidneys were unique in burning circulating citrate while the liver preferred unsaturated over saturated fatty acids. These preferences were confirmed via isotope tracing studies in mice. These findings highlight the value of the comprehensive analysis of inter-organ metabolite exchange for elucidating organismal metabolism.