Overview of research

The development of a functioning nervous system requires that different neurons with specific functions be produced following the execution of precise developmental programs that establish correct neuronal networks. 

In Drosophila, visual information from 800 unit eyes (facets) is processed in distinct brain structures in the optic lobes, each subdivided into 800 matching columns that project in the brain an image of the world perceived by the retina. For instance, motion information is processed in two parallel pathways: T4 neurons from the ON-pathway detect the motion of bright objects in a black background, while T5 neurons from the OFF-pathway process motion of dark objects. T4 and T5 neurons are the first neurons that respond differentially to motion in different directions. There are four subtypes, of T4 and T5, each responding to motion in one of the four cardinal directions (back to front, front to back, up and down), such that all T4 and T5 neurons with the same directional preference project their axons in the same region of the Lobula Plate to support the perception of self-motion.

Pinto Teixeira and colleagues in the laboratory of Claude Desplan in the Center for Genomics and Systems Biology at NYU in Abu Dhabi and the department of biology at NYU in New York asked how each of the 4 subtypes of T4 and T5 neurons is specified and how their precise arrangement is established during development. They discovered that T4/T5 neurons originate from two pools of stem cells, one that produces cells sensitive to horizontal motion, and the other to vertical motion. These stem cells then rely on a novel mode of neurogenesis where two sequential divisions produce sets of two T4 and two T5 neurons with opposite motion direction selectivity, e.g. one T4/T5 pair sensitive to back-to-front and the other to front-to-back. Because T4/T5 neurons with opposite motion direction selectivity are produced by the same stem cell at the same time, these four neurons synchronously innervate the same position in the brain corresponding to a specific point in visual space. Thus, the organization of neuronal projections is an emergent characteristic of this neurogenic program and derives directly from neuronal birth order, illustrating how simple developmental rules can produce complex neural organization. 

Significance of research

This study shows that the program that specifies the identity of the eight T4/T5 neuron subtypes is sufficient to organize the neural circuit that supports global motion perception in the fly. It provides an example of how complex neuronal circuits can be built from simple developmental rules. Understanding how neuronal identities are specified and how neural circuits are build during development leaves us in a better position to understand the development of neurological disorders and draw general principles for the production of stem cell derived neurons and the reconstruction of neural circuits in a therapeutic setting.

Take home message for general public

These findings identify a causal link between the genetic program that specifies the identity of a group of neurons and the neural circuit these neurons form. It provides and example of how a complex neuronal circuit can be built from simple developmental rules.