Axonal transport and growth cone dynamics play a fundamental role for pathfinding and the formation of neuronal networks in the brain. During neuronal development, migrating axons wire the brain by generating long range connections between different brain regions. In the visual system, the retinotopic map connects the retina to the visual centers in the midbrain. When axons from retinal ganglion cells reach the optic tectum (superior colliculus in mammals) they form ordered connections with tectal neurons thereby establishing a topographic map. The map precision is important to correctly transmit the visual information projected onto the retina. Families of ephrin guidance molecule distributed in gradients in the retina and tectum play a crucial role in the map formation process. In addition, engrailed homeoprotein transcription factors are important for axonal guidance. Engrailed displays a graded expression in the chick optic tectum and participates in axonal guidance. Moreover, engrailed regulates the expression of ephrinA5 and increases the sensitivity of growth cones to ephrinA5 repellent activity. The molecular pathway for the engrailed-ephrinA5 interaction involves the internalization of engrailed into the growth cone, which stimulates the production and secretion of ATP, followed by hydrolysis of extracellular ATP into adenosine and the activation of membrane bound adenosine A1 receptor that are present in higher concentrations in temporal than nasal GCs. Based on these findings, we propose a computational model that shows how the synergetic interaction between engrailed and ephrinA5 increases the precision of the map formation.