Overview
 

We are interested in understanding how the nervous system is wired during development.
 
 
The cellular complexity within our nervous systems is staggering, yet our ability to react to changes in the environment relies on the formation of precise connections between neurons. How do neurons navigate cellular complexity and form specific connections in a reproducible manner? 
 
 
We study this question in the Drosophila visual system as it
comprises genetically accessible cell types with well defined
morpholgies and synaptic specificities, and advanced genetic
methods allow interrogation of the mechanisms underlying these
patterns of connections. Our goal is to identify general molecular
principles underlying how neurons form precise connections. 
 
 
Our work focuses on the medulla, a region of the optic lobe
wherein visual information (e.g. motion and color) is processed
within discrete layers. Within the medulla, more than 100 different
neuronal cell types form connections in one or more of ten layers
in a stereotyped manner. While each layer contains synapses
between many neurons, not all neurons in a layer synapse with
each other. Our work concentrates on identifying molecular
determinants that underlie this specificity. We are especially
interested in understanding how neurons use cell recognition
molecules to distinguish between appropriate and inappropriate synaptic partners.
 
 
 
Approach
 
 
Cells, synapses and molecules.
 
We hypothesize that differences in gene expression underlie
alternative patterns of connectivity. Through RNA sequencing
we've identified genes that are differentially expressed by
neurons that innervate the medulla. We find that each neuron
type expresses a unique combination of cell surface molecules
and transcription factors just prior to synapse formation. A major
focus of the lab is to characterize how these genes contribute
to wiring specificity.
 
 
For example, we have discovered two families of heterophilic
cell recognition molecules whose members are expressed in a matching manner between specific synaptic pairs. Using molecular genetics and synaptic tagging methods in combination with light and electron microscopy we are assessing whether and how these genes contribute to
synaptic specificity.
 
 
An additional focus of the lab is to study synapse formation in vivo between
specific synaptic pairs. We have developed tools to visualize endogenous
synaptic proteins in neurons of interest in vivo with single cell resolution
during development. Using these tools we aim to identify cell surface
molecules that regulate interactions between specific partners, and then
understand how downstream signaling coordinates the assembly of synaptic
contacts.
 
 
In general, we use molecular genetics, transcriptomics and microscopy to
understand how specific neurons achieve their unique morphologies and form stereotyped patterns of connections. The advanced genetic tools available for Drosophila and especially for neurons within the visual system allow us to explore neural connectivity during development in vivo with single cell resolution.
 
In the future we plan to incorporate genomics, optogenetics and electrophysiology to complement our transcriptomics experiments and morphological analyses of wiring specificity.