The Developmental Rules of Neural Superposition in Drosophila

Abstract

Summary Complicated neuronal circuits can be genetically encoded, but the underlying developmental algorithms remain largely unknown. Here, we describe a developmental algorithm for the specification of synaptic partner cells through axonal sorting in the Drosophila visual map. Our approach combines intravital imaging of growth cone dynamics in developing brains of intact pupae and data-driven computational modeling. These analyses suggest that three simple rules are sufficient to generate the seemingly complex neural superposition wiring of the fly visual map without an elaborate molecular matchmaking code. Our computational model explains robust and precise wiring in a crowded brain region despite extensive growth cone overlaps and provides a framework for matching molecular mechanisms with the rules they execute. Finally, ordered geometric axon terminal arrangements that are not required for neural superposition are a side product of the developmental algorithm, thus elucidating neural circuit connectivity that remained unexplained based on adult structure and function alone.

Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system

“…This system is similar to one developed by Hiesinger and colleagues to study the cellular mechanism of neural superposition, the choreographed re-distribution of R1-6 growth cones from ommaditial bundles to lamina cartridges (Langen et al, 2015). In the medulla neuropil, Hiesinger and colleagues used ex vivo live imaging to study R7 targeting, specifically characterizing the role of the Ca2+-dependent cell adhesion molecule, N-cadherin, in mediating adhesive interaction between growth cones and the developing neuropil (Özel et al, 2015).…”

Dscam Proteins Direct Dendritic Targeting through Adhesion

“…These synapses are called tetrads and comprise a single presynaptic active zone juxtaposing the postsynaptic elements of an invariant pair of dendrites from L1 and L2 neurons and variable contributions from two other neurons. Circuit assembly in the lamina has been studied using light and electron microscopy, genetics and, more recently, through live imaging (Langen et al, 2015; Meinertzhagen and O’Neil, 1991; Meinertzhagen and Sorra, 2001; Rivera-Alba et al, 2011; see also references below).…”

From the Eye to the Brain

“…Starting around 25h APF, the developing medulla starts to rotate, being pulled by the lamina (White and Kankel 1978, Langen et al 2015), and inserting itself right under the lamina neuropil. By 40h APF, the rotation is complete and the optic lobe has adopted its final configuration which the four neuropils: lamina, medulla, lobula and lobula plate (Claire Bertet, Karl Fischbach personal communications).…”