826C Poster - 13. Neural development and physiology
Saturday April 09, 1:30 PM - 3:30 PM

Genetic mechanisms underlying the development and distribution of Dm4 neurons in the Drosophila medulla


Authors:
Urfa Arain 1; Ted Erclik 1, 2

Affiliations:
1) Cell & Systems Biology, University of Toronto, Toronto, Ontario, Canada ; 2) Biology, University of Toronto, Mississauga, Ontario, Canada

Keywords:
e. neuronal morphogenesis; r. circuits

The Drosophila compound eye is comprised of an array of photoreceptor units that send visual stimuli to the processing centers of the brain. Colour and motion processing occurs in the medulla, which is made up of repeating columnar units that are innervated by over 90 neuronal cell-types. During brain development, a subset of medulla neurons migrate from their spatially restricted birth locations to reach their final positions in the adult retinotopic circuit. To date, little is known about the mechanisms underlying this movement of medulla neurons. To elucidate the mechanisms that regulate this process, we have focused on the migration of a single neuronal cell-type, Dm4. There are approximately 40 Dm4 neurons per medulla, each of which cover ~20 columns across the antero-posterior and dorso-ventral axes of the adult retinotopic field. A single Dm4 neuron sends its axon into the M6 layer of the medulla neuropil, and forms dendritic arbors in the superficial M3 layer to make synaptic contacts with lamina monopolar cells (L3). To understand how these circuits are established, we generated a Dm4-specific split-Gal4 driver that allows us to track the relationship of Dm4 movement with morphological changes during development. We find that Dm4 neurons are born in the mid-third-instar larval brain as a cluster of cells in the medial and ventral region of the developing medulla cortex. Subsequently, during pupal development, Dm4 neurons move across the antero-posterior and dorso-ventral axes. We find that Dm4 neurons initiate their movement across the antero-posterior axis at ~25h APF, followed by their dorso-ventral migration 5 hours later at ~30h APF. We show that Dm4 axons project to their target regions in the medulla neuropil well before migration is initiated, whereas dendritogenesis occurs during migration and is completed by 48h APF. An RNAi-based screen for genes required for Dm4 migration identified the transcription factor Traffic Jam (Tj) as a critical regulator of the process. Loss of tj in Dm4 neurons results in a ventromedial cluster of cells in the adult medulla that failed to migrate across both the antero-posterior and dorso-ventral axes. tj-mutant Dm4 neurons project to the correct target layers in the medulla, but exhibit disorganized dendritic projections in the M3 layer. Strikingly, single-cell clones of tj-mutant Dm4s reveal regional differences in the severity of these defects; cells fated to move a larger distance from their birth location exhibit greater dendritic defects compared to those with shorter migration trajectories. Taken together, our data support a model in which neuronal migration is required for neurons to form proper dendritic connections within their target columns.