Essential Function of the Serine Hydroxymethyl Transferase (SHMT) Gene During Rapid Syncytial Cell Cycles in<i>Drosophila</i>

Abstract

Many metabolic enzymes are evolutionarily highly conserved and serve a central function in the catabolism and anabolism of cells. The serine hydroxymethyl transferase (SHMT) catalyzing the conversion of serine and glycine and vice versa feeds into tetrahydrofolate (THF)-mediated C1 metabolism. We identified a <i>Drosophila</i> mutation in <i>SHMT</i> (CG3011) in a screen for blastoderm mutants. Embryos from <i>SHMT</i> mutant germline clones specifically arrest the cell cycle in interphase 13 at the time of the midblastula transition (MBT) and prior to cellularization. The phenotype is due to a loss of enzymatic activity as it cannot be rescued by an allele with a point mutation in the catalytic center but by an allele based on the <i>SHMT</i> coding sequence from <i>Escherichia coli</i> The onset of zygotic gene expression and degradation of maternal RNAs in <i>SHMT</i> mutant embryos are largely similar to that in wild-type embryos. The specific timing of the defects in <i>SHMT</i> mutants indicates that at least one of the SHMT-dependent metabolites becomes limiting in interphase 13, if it is not produced by the embryo. Our data suggest that mutant eggs contain maternally-provided and SHMT-dependent metabolites in amounts that suffice for early development until interphase 13.