Topography of thalamic projections requires attractive and repulsive functions of Netrin-1 in the ventral telencephalon.
Recent studies have demonstrated that the topography of thalamocortical (TC) axon projections is initiated before they reach the cortex, in the ventral telencephalon (VTel). However, at this point, the molecular mechanisms patterning the topography of TC projections in the VTel remains poorly understood. Here, we show that a long-range, high-rostral to low-caudal gradient of Netrin-1 in the VTel is required in vivo for the topographic sorting of TC axons to distinct cortical domains. We demonstrate that Netrin-1 is a chemoattractant for rostral thalamic axons but functions as a chemorepulsive cue for caudal thalamic axons. In accordance with this model, DCC is expressed in a high-rostromedial to low-caudolateral gradient in the dorsal thalamus (DTh), whereas three Unc5 receptors (Unc5A-C) show graded expression in the reverse orientation. Finally, we show that DCC is required for the attraction of rostromedial thalamic axons to the Netrin-1-rich, anterior part of the VTel, whereas DCC and Unc5A/C receptors are required for the repulsion of caudolateral TC axons from the same Netrin-1-rich region of the VTel. Our results demonstrate that a long-range gradient of Netrin-1 acts as a counteracting force from ephrin-A5 to control the topography of TC projections before they enter the cortex.
Powell
Ashton W
AW
Neuroscience Center, Department of Pharmacology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, United States of America.
Sassa
Takayuki
T
Wu
Yongqin
Y
Tessier-Lavigne
Marc
M
Polleux
Franck
F
D000818:Animals; D001369:Axons / Q000378:metabolism*; D019521:Body Patterning; D002450:Cell Communication; D002630:Chemotactic Factors / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D000075386:Netrin Receptors; D000075388:Netrin-1; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D013687:Telencephalon / Q000196:embryology / Q000378:metabolism*; D013788:Thalamus / Q000166:cytology* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D002630:Chemotactic Factors; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; C000617353:Ntn1 protein, mouse; D017475:Receptors, Nerve Growth Factor; D025521:Tumor Suppressor Proteins; C105653:Unc5c protein, mouse; D000075388:Netrin-1