The question I am asking is, “How do cells get the right shapes and make the right attachments to build organs?”  Single cells have amazing morphologies that determine their function — nowhere more so than in the neurons and glia of our brains.  Defects in cell shape lead to birth defects or, in the nervous system, neuropsychiatric disorders.  Yet much of what we know about cell shape comes from homogeneous cells grown in a dish.

To address this question, my lab uses the tiny worm C. elegans.  In these animals, every cell has been identified and the shapes and connections of each cell have been catalogued — including its 302 neurons and 50 glia.  The fact that these cells develop in such a predictable fashion strongly suggests that there are genetic programs that determine the shape and connections of each cell.  We want to identify these genetic programs.

The main methods we use are microscopy and genetics.  We use microscopy to visualize individual neurons and glia in live, intact animals. We use genetics to identify the genes that are required for these structures to form. With these approaches, we have identified (1) extracellular matrix proteins required for specific neuronal dendrites to anchor to their targets, (2) adhesion molecules required for formation of specific neuron-neuron and neuron-glia attachments, and (3) a transcription factor that controls the identity of specific subtypes of glia. An emerging theme is that many of these neuronal and glial structures are ultimately assembled using epithelial scaffolds.