The novel peptide HEADY specifies apical fate in a simple radially symmetric metazoan

One of the first steps in animal development is axis formation, during whic h an uneven distribution of signals and/or transcription factors results in the establishment of polarity in the embryo. Hydra, one of the simplest me tazoan animals, shows characteristics of a permanent embryo. Even adult pol yps have a striking capacity to regenerate, suggesting that molecular mecha nisms underlying de novo pattern formation are permanently active and self regulatory. Here we show that HEADY, a short, amidated peptide, plays a cen tral role in the specification of apical fate in this simple metazoan. The HEADY gene, whose transcripts accumulate at the apical organizing center, i s required for specification of apical fate, as disruption of HEADY functio n by dsRNA mediated interference (RNAi) results in severe defects in head f ormation. Conversely, an instructive role of HEADY in head specification is demonstrated by the application of synthetic HEADY peptide, which induces formation of secondary axes with head morphology. Thus, the HEADY peptide a cts as developmental switch to pattern the apical-basal axis of Hydra, prov iding a first insight into how initial asymmetry is specified in lower meta zoan animals.