A molecular mechanism regulating the timing of corticogeniculate innervation
Justin M. Brooks1,3, Jianmin Su1, Carl Levy2, Jessica S. Wang3, Tania A. Seabrook3,4, William Guido3,4, Michael A. Fox1,2,3*
Neural circuit formation demands precise timing of innervation by different classes of axons, however the mechanisms underlying such activity remain largely unknown. In the dorsal lateral geniculate nucleus (dLGN), axons from retina and visual cortex innervate thalamic relay neurons in a highly coordinated manner, with those from the cortex arriving well after those from retina. The differential timing of retino- and corticogeniculate innervation is not a coincidence but is orchestrated by retinal inputs. Here, we identified a chondroitin sulfate proteoglycan (CSPG) that regulates the timing of corticogeniculate innervation. Aggrecan, a repulsive CSPG, is enriched in neonatal dLGN and inhibits cortical axons from prematurely entering dLGN. Postnatal loss of aggrecan from dLGN coincides with upregulation of aggrecanase expression in dLGN and corticogeniculate innervation and, importantly, is regulated by retinal inputs. Taken together, these studies reveal a molecular mechanism by which one class of axons coordinates the temporal targeting of another class of axons.