Title: Circuit transcription factors in Caenorhabditis elegans
Description: Many neuronal patterning genes are expressed in distinct populations of cells in the nervous system, leading researchers to analyze their function in specific isolated cellular contexts that often obscure broader, themes of gene function. In this thesis, I aim to make clearer those overlooked common functional themes. I show that the C. elegans homeobox gene unc-42 is expressed in 15 out of a total of 118 distinct sensory, inter, and motor neuron classes throughout the C. elegans nervous system. Of these 15 unc-42(+) synaptically interconnected neuron classes, I show the extent to which unc-42 controls their identities and assembly into functional circuitry. I find that unc-42 defines the routes of communication between these interconnected neurons by controlling the expression of neurotransmitter pathway genes, neurotransmitter receptors, neuropeptides and neuropeptide receptors. I also show that unc-42 controls the expression of molecules involved in axon pathfinding and cell-cell recognition.

Consequently, I show how the loss of unc-42 has effects on axon pathfinding and chemical synaptic connectivity, as determined by electron microscopical reconstruction of serial sections of unc-42 mutants. I conclude that unc-42 plays a critical role in establishing functional circuitry by acting as a terminal selector of functionally connected neuron types. I speculate that in other parts of the nervous system “circuit transcription factors” may also control assembly of functional circuitry and propose that such organizational properties of transcription factors may be reflective of not only an ontogenetic, but perhaps also phylogenetic trajectory of neuronal circuit establishment.