First Author | Jaworski A | Year | 2015 |
Journal | Science | Volume | 350 |
Issue | 6263 | Pages | 961-5 |
PubMed ID | 26586761 | Mgi Jnum | J:227045 |
Mgi Id | MGI:5699613 | Doi | 10.1126/science.aad2615 |
Citation | Jaworski A, et al. (2015) Operational redundancy in axon guidance through the multifunctional receptor Robo3 and its ligand NELL2. Science 350(6263):961-5 |
abstractText | 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. |