The LRR receptor Islr2 is required for retinal axon routing at the vertebrate optic chiasm.
BACKGROUND
In the visual system of most binocular vertebrates, the axons of retinal ganglion cells (RGCs) diverge at the diencephalic midline and extend to targets on both ipsi- and contralateral sides of the brain. While a molecular mechanism explaining ipsilateral guidance decisions has been characterized, less is known of how RGC axons cross the midline.


RESULTS
Here, we took advantage of the zebrafish, in which all RGC axons project contralaterally at the optic chiasm, to characterize Islr2 as an RGC receptor required for complete retinal axon midline crossing. We used a systematic extracellular protein-protein interaction screening assay to identify two Vasorin paralogs, Vasna and Vasnb, as specific Islr2 ligands. Antibodies against Vasna and Vasnb reveal cellular populations surrounding the retinal axon pathway, suggesting the involvement of these proteins in guidance decisions made by axons of the optic nerve. Specifically, Vasnb marks the membranes of a cellular barricade located anteriorly to the optic chiasm, a structure termed the "glial knot" in higher vertebrates. Loss of function mutations in either vasorin paralog, individually or combined, however, do not exhibit an overt retinal axon projection phenotype, suggesting that additional midline factors, acting either independently or redundantly, compensate for their loss. Analysis of Islr2 knockout mice supports a scenario in which Islr2 controls the coherence of RGC axons through the ventral midline and optic tract.


CONCLUSIONS
Although stereotypic guidance of RGC axons at the vertebrate optic chiasm is controlled by multiple, redundant mechanisms, and despite the differences in ventral diencephalic tissue architecture, we identify a novel role for the LRR receptor Islr2 in ensuring proper axon navigation at the optic chiasm of both zebrafish and mouse.
Max-Planck-Institut für Entwicklungsbiologie, Abteilung Genetik, Spemannstraße 35, 72076, Tübingen, Germany. paolo.panza@tuebingen.mpg.de.
Paolo
P
Panza
Department of Neuroscience, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY, 10032, USA.
Austen A
AA
Sitko
Max-Planck-Institut für Entwicklungsbiologie, Abteilung Genetik, Spemannstraße 35, 72076, Tübingen, Germany.|Present address: Max-Planck-Institut für Herz- und Lungenforschung, Abteilung Genetik der Entwicklung, Ludwigstraße 43, 61231, Bad Nauheim, Germany.
Hans-Martin
HM
Maischein
Max-Planck-Institut für Entwicklungsbiologie, Elektronenmikroskopie, Spemannstraße 35, 72076, Tübingen, Germany.
Iris
I
Koch
Max-Planck-Institut für Entwicklungsbiologie, Elektronenmikroskopie, Spemannstraße 35, 72076, Tübingen, Germany.
Matthias
M
Flötenmeyer
Wellcome Trust Sanger Institute, Cell Surface Signalling Laboratory, Hinxton, Cambridge, CB10 1HH, UK.
Gavin J
GJ
Wright
Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
Kenji
K
Mandai
Department of Pathology & Cell Biology, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY, 10032, USA.|Department of Neuroscience, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY, 10032, USA.
Carol A
CA
Mason
Max-Planck-Institut für Entwicklungsbiologie, Abteilung Genetik, Spemannstraße 35, 72076, Tübingen, Germany.
Christian
C
Söllner
D000818:Animals; D001369:Axons / Q000378:metabolism*; D019521:Body Patterning / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009897:Optic Chiasm / Q000196:embryology*; D012160:Retina / Q000196:embryology*; D014795:Visual Pathways / Q000196:embryology; D015027:Zebrafish
C544153:Linx protein, mouse; D009419:Nerve Tissue Proteins