A Common Origin for the NT Superfamily Underlies Nervous System Structure and Function
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(A) NT superfamily members identified in protostomes (Drosophila) and deuterostomes (vertebrates, Amphioxus, sea urchin, and acorn worm) imply that NTs were present in Urbilateria, their common ancestor. A protostomian NT gene would have duplicated to give rise to DNT1, DNT2, and spz in insects or perhaps earlier. A chordate NT duplicated twice to give rise to the four vertebrate NTs, and the NGF ortholog duplicated again in fish to result in NT6/7. Identified Trk and p75 receptors are also shown; Trk-like receptors lack some extracellular domains. NT receptors and signalling mechanisms may have diversified through evolution. Annelids, flatworms, nematodes, and tunicates are not shown, see Figure S1.
(B) Hypothesis that the NTs are required in all centralised nervous systems to link structure and function. NTs are also present at least in acorn worm with a nerve net, a diffuse nervous system, where NT may play a subset of functions, suggesting that NTs could also be present in lower animals (e.g., Cnidarians). Drosophila can be used as a model system for NT-related studies.