VEGF shows its attractive side at the midline

Abstract

Vascular endothelial growth factor (VEGF) family members are best known for their powerful mitotic and angiogenic activities toward endothelial cells. Two independent studies in this issue of Neuron now provide compelling evidence that VEGF-A secreted at the CNS midline functions as an attractant for developing axons of spinal commissural neurons and contralaterally projecting retinal ganglion cells.

Figure 1

(A) Embryonic spinal cord showing trajectory of commissural axons. Pre-crossing spinal commissural axons are initially pushed ventrally by roof plate-derived inhibitory cues, including BMPs and Draxin (red gradient). Chemoattractants secreted by the floor plate include Netrin-1, Shh, and VEGF (green gradient). After crossing the midline, commissural axons lose attraction to Netrin-1 and Shh. Conversely, factors such as Slits, Sema3B, and Sema3F, which have no effect on commissural axons before crossing, become potent repellents after crossing. (B) In vertebrates with frontally located eyes, subpopulations of RGC axons are segregated at the optic chiasm to project to targets on both the ipsilateral and contralateral side of the brain. EphrinB2 and Shh at the chiasm midline are repellents for EphB1- and Boc-expressing RGCs destined for the ipsilateral optic tract. NrCAM expressed by RGCs is required in a small subset of late born neurons to form contralateral projections. The VEGF-A isoform VEGF164 is expressed at the midline where it functions as a chemoattractant for Npn-1-positive RGCs to instruct contralateral growth. (D, dorsal; V, ventral; N, nasal; T, temporal retina).