Operational redundancy in axon guidance through the multifunctional receptor Robo3 and its ligand NELL2

Science  20 Nov 2015:
Vol. 350, Issue 6263, pp. 961-965
DOI: 10.1126/science.aad2615

You are currently viewing the abstract.

View Full Text

Via your Institution

Log in through your institution

Log in through your institution

No going back

The mammalian spinal cord coordinates neuronal systems across the body. Axons that cross the spinal cord midline during development first need permission to cross and then instruction not to keep crossing back and forth. Jaworski et al. studied the axonal guidance receptor ROBO3 and found a ligand NELL2 in mice that appears to help in this process.

Science, this issue p. 961


Axon pathfinding is orchestrated by numerous guidance cues, including Slits and their Robo receptors, but it remains unclear how information from multiple cues is integrated or filtered. Robo3, a Robo family member, allows commissural axons to reach and cross the spinal cord midline by antagonizing Robo1/2–mediated repulsion from midline-expressed Slits and potentiating deleted in colorectal cancer (DCC)–mediated midline attraction to Netrin-1, but without binding either Slits or Netrins. We identified a secreted Robo3 ligand, neural epidermal growth factor-like-like 2 (NELL2), which repels mouse commissural axons through Robo3 and helps steer them to the midline. These findings identify NELL2 as an axon guidance cue and establish Robo3 as a multifunctional regulator of pathfinding that simultaneously mediates NELL2 repulsion, inhibits Slit repulsion, and facilitates Netrin attraction to achieve a common guidance purpose.

View Full Text