In stark contrast to the rapid morphological radiation of eumetazoans during the Cambrian explosion, the simple body plan of sponges (Phylum Porifera) emerged from the Cambrian relatively unchanged. Although the genetic and developmental underpinnings of these disparate evolutionary outcomes are unknown, comparisons between modern sponges and eumetazoans promise to reveal the extent to which critical genetic factors were present in their common ancestors. Two particularly interesting classes of genes in this respect are those involved in cell signaling and adhesion. These genes help guide development and morphogenesis in modern eumetazoans, but the timing and sequence of their origins is unknown. Here, we demonstrate that the sponge Oscarella carmela, one of the earliest branching animals, expresses core components of the Wnt, transforming growth factor , receptor tyrosine kinase, Notch, Hedgehog, and Jak͞Stat signaling pathways. Furthermore, we identify sponge homologs of nearly every major eumetazoan cell-adhesion gene family, including those that encode cell-surface receptors, cytoplasmic linkers, and extracellular-matrix proteins. From these data, we infer that key signaling and adhesion genes were in place early in animal evolution, before the divergence of sponge and eumetazoan lineages.eumetazoa ͉ porifera ͉ Cambrian explosion ͉ homoscleromorpha ͉ Oscarella T he fossil record from Ϸ540 Mya documents the abrupt appearance of fully diversified eumetazoan body plans during the ''Cambrian explosion.'' In contrast, fossil evidence of sponges dates to Ϸ580 Mya and reveals that their simple body plan predates the Cambrian and has since remained relatively unchanged (1, 2). Although extrinsic environmental factors have received much attention as the driving force behind the Cambrian explosion (3), the disparate outcomes in lineages leading to modern sponges and eumetazoans point to intrinsic genetic differences. Intrinsic factors that potentially contributed to the selective morphological diversification of eumetazoans include the evolution of developmentally important gene families, signaling pathways, or regulatory elements and linkages in their ancestors. A key to illuminating how intrinsic factors contributed to the Cambrian explosion will be to reconstruct the evolutionary sequence of origination, elaboration, and assembly of developmentally important gene families into interacting pathways and networks.Modern sponges promise to offer critical insights into the earliest events in animal genome evolution. The fossil record of sponges predates that of all other animal groups (2), and phylogenetic analyses support sponges as an outgroup of all eumetazoan phyla (4). Indeed, recent studies indicate that sponges are paraphyletic (5-9) and that eumetazoans evolved from a sponge-like ancestor (9). Among the major sponge groups, the homoscleromorphs (Fig. 1b) have particular relevance to the study of eumetazoan origins and evolution. Although of uncertain phylogenetic position (10, 11), homoscleromorphs are thought ...