Figure 6.

Graded expression of Engrailed guides retinotectal axons. A. Axons originating from the retina within a temporal-to-nasal EphA2 gradient project onto the tectum within posterior to anterior En1/2 and EphrinA5 gradients. Temporal retinotectal growth cones remain within the anterior tectum while nasal growth cones are attracted to posterior tectum. B. Ectopic expression of En1/2 within anterior tectum results in local repulsion and attraction of temporal and nasal growth cones, respectively (Drescher et al., 1997; Friedman and O’Leary, 1996; Itasaki and Nakamura, 1996; Logan et al., 1996; Shigetani et al., 1997). C. Local expression of secreted single-chain antibody against En1/2 disrupts axon guidance in vivo and results in overgrowth of temporal growth cones that invade the posterior tectum (Wizenmann et al., 2009). D. In vitro guidance assays show that En1/2 attracts nasal growth cones and repels temporal growth cones. This activity is in part local as shown by the attraction and repulsion of nasal and temporal growth cones separated from their cell bodies (Brunet et al., 2005). E. The local activity of En1/2 acts in part through mTOR-dependent translation and results in expression mitochondrial proteins. This activity has local effects on mitochondria, cytoskeleton and other unidentified targets leading to remote effects in the nucleus. En1/2 might also undergo retrograde transport to participate in regulating remote nuclear activity such as transcription and epigenetic events.