Homeobox Genes and Neuron Identity Control on a Brain-Wide Level

PROJECT SUMMARY While common, evolutionarily conserved themes of early neuronal patterning in the developing embryo have emerged over the years, there are, as of now, no firmly proven, common organizational themes for how neuron acquire and maintain their terminally differentiated state. We propose to probe here existence of such a common organizational principle, by testing the hypothesis that each neuron class of the nematode C. elegans is functionally specified by members of a specific family of transcription factors, the homeodomain-type transcription factors. We test this hypothesis by using rigorous genetic loss of function analysis, using mutant alleles of all 70 conserved homeobox genes and using a multicolor bar coding scheme, through which we visualize the differentiated state of all neurons throughout the nervous system. The finding that homeodomain transcription factors control the identity of all neurons in a simple nervous system would have wide-ranging implications for our understanding of evolution of the nervous system and may provide explicit directions for how to classify and then functionally study neuron classes in mammalian nervous systems.