Optic chiasm presentation of Semaphorin6D in the context of Plexin-A1 and Nr-CAM promotes retinal axon midline crossing.
At the optic chiasm, retinal ganglion cells (RGCs) project ipsi- or contralaterally to establish the circuitry for binocular vision. Ipsilateral guidance programs have been characterized, but contralateral guidance programs are not well understood. Here, we identify a tripartite molecular system for contralateral RGC projections: Semaphorin6D (Sema6D) and Nr-CAM are expressed on midline radial glia and Plexin-A1 on chiasm neurons, and Plexin-A1 and Nr-CAM are also expressed on contralateral RGCs. Sema6D is repulsive to contralateral RGCs, but Sema6D in combination with Nr-CAM and Plexin-A1 converts repulsion to growth promotion. Nr-CAM functions as a receptor for Sema6D. Sema6D, Plexin-A1, and Nr-CAM are all required for efficient RGC decussation at the optic chiasm. These findings suggest a mechanism by which a complex of Sema6D, Nr-CAM, and Plexin-A1 at the chiasm midline alters the sign of Sema6D and signals Nr-CAM/Plexin-A1 receptors on RGCs to implement the contralateral RGC projection.
Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Takaaki
T
Kuwajima
Yutaka
Y
Yoshida
Noriko
N
Takegahara
Timothy J
TJ
Petros
Atsushi
A
Kumanogoh
Thomas M
TM
Jessell
Takeshi
T
Sakurai
Carol
C
Mason
D000818:Animals; D001369:Axons / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009897:Optic Chiasm / Q000166:cytology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D039961:Semaphorins / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D009419:Nerve Tissue Proteins; C491151:Nrcam protein, mouse; C492114:Plxna1 protein, mouse; D011956:Receptors, Cell Surface; C483479:Sema6d protein, mouse; D039961:Semaphorins