The Miller lab focuses on the genetic mechanisms of neural development, specifically on how genetic programs define synaptic specificity in the nervous system, a phenomenon of fundamental importance to the creation of functional circuits in the brain.  With its simple, well-defined nervous system and powerful genetics, the nematode C. elegans is an especially appropriate model system. 

The lab has shown that the UNC-4 homeodomain protein and its transcriptional cofactor UNC-37/Groucho function together to define the specificity of synaptic inputs to a single class of motor neurons in the C. elegans ventral nerve cord.  They then developed innovative microarray-based approaches to identify UNC-4 target genes in this pathway.  One target encodes the homeodomain protein, CEH-12, the nematode homolog of HB9, a key determinant of motor neuron fate in flies, birds, and mammals.  This striking result argues that the mechanisms of synaptic specificity controlling the nematode motor circuit are also implemented in the vertebrate spinal cord, thereby indicating that the use of C. elegans can reveal key determinants of synaptic specificity in more complex nervous systems that would be difficult to identify by direct approaches in those complex systems. 

RECENT PUBLICATIONS

UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans. 2007 Genes & Development 21:332-346

Computational inference of the molecular logic for synaptic connectivity in C. elegans.  2006 Bioinformatics 22:e497-506

The motor circuit.  2006 International Review of Neurobiology 69:125-167