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  • Title: Operational redundancy in axon guidance through the multifunctional receptor Robo3 and its ligand NELL2.
    Author: Jaworski A, Tom I, Tong RK, Gildea HK, Koch AW, Gonzalez LC, Tessier-Lavigne M.
    Journal: Science; 2015 Nov 20; 350(6263):961-5. PubMed ID: 26586761.
    Abstract:
    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.
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