Paracrine and juxtacrine signaling via proteins expressed on the cell surface are an integral part of metazoan biology. More
than one-half billion years ago epidermal growth factor (EGF) and its cognate receptor formed a functional binding partnership, which
has been conserved through evolution in essentially all eubilaterate members of the animal kingdom. Early chordates spawned offspring
of these seminal genes to begin the creation of new gene families and an expanded cell-cell signaling network, which included the
Neuregulin (NRG) ligands and the erbB receptors. First appearance of ancestral NRG, represented in a NRG4-like gene in the lancelet
Branchiostoma floridae, appears to have: 1) occurred in the common chordate ancestor prior to the divergence of lancelets (amphioxus),
and; 2) antedated the formation of the receptor gene family. Orthologues of NRG1 and multiple erbB receptors found in the sea lamprey
Petromyzon marinus suggest that several key events, which were required to expand and diversify these gene families, occurred in the
common ancestor of agnathostomes and jawed vertebrates. These important inventions surely played major roles in the acquisition of
multiple apomorphic features of the emerging vertebrate lineage.
Keywords: Binding, erbB receptor, lamprey, lancelet.
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