Robo1 and Robo2 cooperate to control the guidance of major axonal tracts in the mammalian forebrain.
The function of the nervous system depends on the precision of axon wiring during development. Previous studies have demonstrated that Slits, a family of secreted chemorepellent proteins, are crucial for the proper development of several major forebrain tracts. Mice deficient in Slit2 or, even more so, in both Slit1 and Slit2 have defects in multiple axonal pathways, including corticofugal, thalamocortical, and callosal connections. In the spinal cord, members of the Robo family of proteins help mediate the function of Slits, but the relative contribution of these receptors to the guidance of forebrain projections remains to be determined. In the present study, we addressed the function of Robo1 and Robo2 in the guidance of forebrain projections by analyzing Robo1-, Robo2-, and Robo1;Robo2-deficient mice. Mice deficient in Robo2 and, more dramatically, in both Robo1 and Robo2, display prominent axon guidance errors in the development of corticofugal, thalamocortical, and corticocortical callosal connections. Our results demonstrate that Robo1 and Robo2 mostly cooperate to mediate the function of Slit proteins in guiding the major forebrain projections.
López-Bendito
Guillermina
G
Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, 03550 Sant Joan d'Alacant, Spain.
Flames
Nuria
N
Ma
Le
L
Fouquet
Coralie
C
Di Meglio
Thomas
T
Chedotal
Alain
A
Tessier-Lavigne
Marc
M
Marín
Oscar
O
D000818:Animals; D001369:Axons / Q000378:metabolism*; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000172:deficiency / Q000378:metabolism*; D013788:Thalamus / Q000196:embryology* / Q000378:metabolism; D000097905:Roundabout Proteins
D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C498888:Robo2 protein, mouse