The recent annotation of basal metazoan genomes [11, 18, 19 and 20] has revealed part lists of important neural modules that allow step-wise tracking of their evolutionary emergence. In this exercise, the modules of the chemical synapse are of particular interest as they allow tracking the origin of bona fide neurons, defined by their capacity to signal to individual target cells via synapses (Figure 1a). Surprisingly, multiple Ku-0059436 clinical trial genes encoding proteins of the highly complex postsynaptic density have recently been traced back to the choanoflagellate-metazoan ancestor [10]. As synapses are obviously absent in choanoflagellates (and in sponges and placozoans), these data

indicate that, in early metazoans, this module must have served another function, before it became part of the synapse. Intriguingly, other studies suggest that the postsynaptic module indeed first acted as a ‘chemosensory module’ [21, 22, 23 and 24]: Initially sensing environmental cues (such as the amino acid glutamate indicating

prey) the partaking receptors and ion channels may have started to receive internal information (such as the transmitter glutamate) from within the newly evolving synapse. Figure 2 illustrates how the postsynapse might have evolved from the chemosensory module [24]. In this scenario, the resulting sensory cell and neuron represent sister cell types; the different usage of chemosensory apparatus and postsynapse

represents www.selleckchem.com/products/PLX-4032.html a divergence of function; and the specialization on sensory versus integrative functions is a division of labour event. Corroborating this scenario, ionotropic glutamate receptor families existed Terminal deoxynucleotidyl transferase before the divergence of animals and plants and metabotropic glutamate (and GABA) receptors predate the metazoan radiation [11 and 12•] (Figure 1a); and, notably, both families are known to comprise chemosensors for external glutamate [25, 26 and 27]. If, as these studies suggest, the postsynaptic module evolved from an ancient chemosensory module, when did this happen? The key step here seems to be the emergence of Neuroligin (Nlgn), the ligand mediating the ‘handshake’ between pre- and postsynaptic neurons on the post-synaptic side. Nlgn has not been found in basal metazoans that lack neurons such as sponges [ 18 and 28] and the placozoan Trichoplax [ 10 and 11], while it is present in the sea anemone Nematostella that possesses neurons [ 10 and 28]. However, to illustrate a caveat of presence/absence analyses, Nlgn has not been found in the freshwater polyp Hydra, which possesses neurons [ 10]. As Hydra belongs to the cnidarians, this absence is necessarily due to secondary loss or strong modification (or the gene simply has not been found yet). The same might be true for the comb jelly Mnemiopsis that likewise possesses neurons with highly characteristic synapses [ 29] but apparently misses Nlgn.