Although homeoprotein transcription factors are best known as cell-autonomous developmental regulators, several homeoproteins have direct non-cell-autonomous activities in the developing vertebrate nervous system. But do homeoproteins also act as signalling molecules during invertebrate development? On p. 2315, Alain Joliot, Florence Maschat and co-workers present the first in vivo evidence for homeoprotein signalling in Drosophila. They use detergent-free immunostaining to reveal an extracellular pool of the homeoprotein Engrailed (En) in the fly wing disc. They then use a secreted single-chain anti-En antibody to show that En is a short-range signalling molecule that participates in the development of the wing's anterior crossvein. Finally, they report that, in contrast to the repressive effect of En on decapentaplegic (dpp) expression, where it acts intracellularly as a transcription factor, extracellular En activity helps to form the anterior crossvein by enhancing Dpp signalling. The researchers propose, therefore, that direct signalling by homeoproteins is an evolutionarily conserved mechanism that is involved in the development of multiple tissue types.