Gradients of Recognition Molecules Shape Synaptic Specificity of a 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 convert object location and motion into directional behaviors downstream through a synaptic gradient mechanism ⁵ . However, the molecular origins of such graded connectivity remain unknown. We addressed this question in a VPN cell type called LPLC2 ⁶ , which integrates looming motion and transforms it into an escape response through two parallel 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 escape ⁷ . 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 control differential synaptic connectivity, enabling the accurate transformation of visual features into motor commands. As within-neuronal-type continuous variation in gene expression is also observed in the mammalian brain ⁸ , graded expression of cell recognition molecules may represent a common mechanism underlying synaptic specificity.