During gastrulation in Drosophila embryos, mesoderm cells invaginate and then spread evenly over the ectoderm. Even spreading is essential for the patterning of the mesoderm by ectodermal signals but is defective in embryos mutant for the RNA-binding protein Held out wings (HOW). Now, on p. 3473,Toledano-Katchalski and co-workers report that HOW regulates mesoderm spreading in a novel manner - by downregulating several mRNA species. The researchers used microarray screening to identify four mRNAs with increased mesodermal expression in how mutant embryos early in development - a time when only the HOW(L) isoform (a post-transcriptional repressor) is expressed. All four mRNAs bind specifically to HOW via their 3′UTRs, an interaction that leads to mRNA degradation. Overexpression of one of the mRNAs- miple, the Drosophila homolog of midkine and pleiotrophin(vertebrate proteins involved in cell migration) - causes mesoderm spreading defects and scattered activation of MAPK in mesodermal cells. Many tissues express HOW(L) and its vertebrate homolog quaking (QKI) early in development,so repression of specific RNAs might be an important developmental control mechanism.