Examining the co-expression matrix of individual genes encoding neurotransmitter enzymes, vesicular and reuptake transporters, and neuropeptides, we found stereotyped combinatorial patterns assigned to specific compartments of the nervous system (Figure S6C). This analysis demonstrates how the rules governing gene co-expression can vary between brain regions. For example, somatostatin (Sst) is a canonical marker of inhibitory neuronal subtypes in the forebrain but was widely expressed in excitatory neurons in the spinal cord, hindbrain, and di-mesencephalon. Moreover, Sst was also expressed in combination with Fev (serotonin, hindbrain), Dbh (noradrenalin, PNS), or the neuropeptide Trh (hypothalamus). In contrast, Pvalb—another canonical marker of forebrain inhibitory cells—was also expressed in excitatory neurons in the mid- and hindbrain. These results demonstrate that neuropeptides, neurotransmitters, calcium-binding proteins, and other neuronal molecules are used in a highly modular fashion and serve different functions in different contexts.
