Gradients of Cell Recognition Molecules Wire Visuomotor Transformation

Converting sensory information into motor commands is fundamental to most of our actions^1,2. In Drosophila, visuomotor transformations are mediated by Visual Projection Neurons (VPNs)^3,4. These neurons encode object location and motion to drive directional behaviors through a synaptic gradient mechanism⁵. However, the molecular origins of such graded connectivity remain unknown. We addressed this question in a VPN cell type called LPLC2⁶, which integrates looming motion and transforms it into an escape response through two separate dorsoventral synaptic gradients at its inputs and outputs. We identified two corresponding dorsoventral expression gradients of cell recognition molecules within the LPLC2 population that regulate this synaptic connectivity. Dpr13 determines synaptic outputs of LPLC2 axons by interacting with its binding partner, DIP-ε, expressed in the Giant Fiber - a neuron that mediates escape⁷. Similarly, Beat-VI regulates synaptic inputs onto LPLC2 dendrites by interacting with Side-II expressed in upstream motion-detecting neurons. Behavioral, physiological, and molecular experiments demonstrate that these coordinated molecular gradients regulate synaptic connectivity, enabling the accurate transformation of visual features into motor commands. As continuous variation in gene expression within a neuronal type is also observed in the mammalian brain⁸, graded expression of cell recognition molecules may represent a common mechanism underlying synaptic specificity.