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

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.

• Authors: Alexander Jaworski, Irene Tom, Raymond K Tong, Holly K Gildea, Alexander W Koch, Lino C Gonzalez, Marc Tessier-Lavigne
• Journal: Science (New York, N.Y.) (Science) Vol. 350 Issue 6263 Pg. 961-5 (Nov 20 2015) ISSN: 1095-9203 [Electronic] United States
• PMID: 26586761 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Association for the Advancement of Science.

Chemical References

• Ligands
• Membrane Proteins
• Nell2 protein, mouse
• Nerve Growth Factors
• Nerve Tissue Proteins
• Ntn1 protein, mouse
• Receptors, Cell Surface
• Receptors, Immunologic
• Robo2 protein, mouse
• Robo3 protein, mouse
• Slit1 protein, mouse
• Tumor Suppressor Proteins
• roundabout protein
• Netrin-1

Topics

• Animals
• Axons (metabolism, physiology)
• Ligands
• Membrane Proteins (genetics, metabolism)
• Mice
• Mice, Mutant Strains
• Nerve Growth Factors (metabolism)
• Nerve Tissue Proteins (genetics, metabolism)
• Netrin-1
• Neurogenesis (genetics, physiology)
• Receptors, Cell Surface
• Receptors, Immunologic (metabolism)
• Spinal Cord (embryology)
• Tumor Suppressor Proteins (metabolism)