Nucleotide sequences encoding orthologs of neurotrophins and their receptors, p75(NTR) and Trk receptors, have been identified in the sea urchin Strongylocentrotus purpuratus, and the acorn worm, Saccoglossus kowalevskii, whereas the ascidian (sea squirt) species Ciona intestinalis and Ciona savignii appear to lack such orthologs. These results suggest that a functional neurotrophin system was already present at the beginning of deuterostome evolution, but was lost in ascidians. Remarkably, it appears that evolution of a p75(NTR) ortholog represented one of the earliest events in the expansion of the tumor necrosis factor receptor superfamily.