Topography of Thalamic Projections Requires Attractive and Repulsive Functions of Netrin-1 in the Ventral Telencephalon
Figure 11
Model of the Role of Netrin-1 Signaling in the Topography of Thalamocortical Projections in the Ventral Telencephalon
Schemas summarizing previous [11] and present findings regarding the axon guidance cues controlling the topographic sorting of TC axons in the VTel.
(A) High rostromedial and low caudolateral gradient of EphA receptors (EphA3-4-7) mediate chemopulsion of rostromedial DTh (DT) axons to the high-caudal to low-rostral gradient of ephrin-A5 in the VTel.
(B and C). In the present study, we demonstrate that a high-rostral to low-caudal gradient of Netrin-1 in the VTel plays a critical role in the topographic projection of DTh axons in the VTel. We show that the rostromedial domain of the DTh expresses high levels of DCC and that the caudolateral domain of the DTh expresses low levels of DCC, which is required both for the attraction of DTR axons and the repulsion of DTC axons to the Netrin-1–rich rostral domain of the VTel. We also show that Unc5A and B are expressed preferentially in the caudolateral domain of the DT, and Unc5C is expressed in a high-caudolateral to low-rostromedial gradient in the DTh. Finally, we provide evidence that (1) Unc5A/C are required for the repulsion of caudal DTh axons from the Netrin-1–rich domain of the VTel, but (2) they do not play any significant role in the projection of rostromedial DTh axons, and (3) that overexpression of Unc5C in DTR axons is sufficient to convert their outgrowth into DTC outgrowth, i.e., repulsion away from the Netrin-1–rich rostral domain of the VTel.
A1, primary auditory area; GE, ganglionic eminence; M1, primary motor area; S1, primary somatosensory area; V1, primary visual area.