S. Lawrence Zipursky, PhD
Distinguished Professor, Biological Chemistry
University of California, Los Angeles
Host: Thomas Clandinin
Neural circuits comprise diverse neuronal cell types interconnected by specific patterns of synapses. The intricacy and specificity of connectivity in brains of both vertebrates and invertebrates are astounding. It is generally believed that specificity arises through two sequential processes, an initial stage of hard wiring driven by genetic programs followed by further sculpting by experience. My talk will focus on genetic programs regulating the hard wiring of neural circuitry. The talk will be in three parts. In the first, I will review the role of self-non-self discrimination between neurites and the phenomenon of self-avoidance in circuit assembly in Drosophila. This is regulated by a remarkable molecular strategy relying on thousands of different isoforms of Dscam1, an immunoglobulin (Ig) containing superfamily protein. I will compare this with recent findings in mammals uncovering a similar, yet distinct molecular strategy regulating self-avoidance through the activity of clustered protocadherins. In the second, I will describe our efforts to uncover the molecular basis of synaptic specificity. Here I will describe the matched expression of two families of Ig-containing cell recognition proteins, DIPs and Dprs, on synaptic partners and the role of these proteins in regulating wiring in the Drosophila visual system. And finally, I will describe recent studies highlighting widespread robust neuron-specific stimulus-independent neural activity in the developing fly brain as neurons form synapses. This type of activity has long been known to regulate wiring in the mammalian retina. These recent findings in Drosophila suggest that stimulus independent neural activity may play an evolutionarily conserved role neural circuit development in both invertebrate and vertebrate brains.
 Shuwa Xu, Qi Xiao, Filip Cosmanescu, Alina P.Sergeeva, Juyoun Yoo, Ying Lin, Phinikoula S. Katsamba, Goran Ahlsen, Jonathan Kaufman, Nikhil T. Linaval, Pei-Tseng Lee, Hugo J.Bellen, Lawrence Shapiro, Barry Honig, Liming Tan, S. Lawrence Zipursky. Interactions between the Ig-Superfamily Proteins DIP-α and Dpr6/10 Regulate Assembly of Neural Circuits. Neuron Volume 100, Issue 6, 19 December 2018, Pages 1369-1384.e6. DOI: 10.1016/j.neuron.2018.11.001
 Akin O, Bajar BT, Keles MF, Frye MA, Zipursky SL. Cell-type-Specific Patterned Stimulus-Independent Neuronal Activity in the Drosophila Visual System during Synapse Formation. Neuron. 2019 Mar 6;101(5):894-904.e5. doi: 10.1016/j.neuron.2019.01.008. Epub 2019 Jan 30. DOI: 10.1016/j.neuron.2019.01.008