Generation of Neuronal Diversity: Analogies and Homologies with Hematopoiesis

The immense variety of neuronal phenotypes in the vertebrate nervous system is apparent in considering just the process of chemical transmission. There are approximately 12 known classical neurotransmitters and more than 30 neuropeptides thus far identified, and individual neurons simultaneously synthesize, store, and secrete one or more classical transmitters in addition to three or more neuropeptides. The transmitters and peptides are expressed in an exceedingly large number of different combinations in different parts of the nervous system. Although there are useful generalizations as to the frequency of certain transmitter-peptide combinations, there are innumerable exceptions to these rules. How the particular combinations produced in each neuron are specified during development is a challenging question. The magnitude of this problem becomes clear if one calculates the number of possible combinations if a neuron is to produce 2 transmitters out of a possible 12 and 3 peptides out of a possible 30. There are 267,960 different potential phenotypes in this example.