title: Reelin is required for class-specific retinogeniculate targeting.
abstract: Development of visual system circuitry requires the formation of precise synaptic connections between neurons in the retina and brain. For example, axons from retinal ganglion cells (RGCs) form synapses onto neurons within subnuclei of the lateral geniculate nucleus (LGN) [i.e., the dorsal LGN (dLGN), ventral LGN (vLGN), and intergeniculate leaflet (IGL)]. Distinct classes of RGCs project to these subnuclei: the dLGN is innervated by image-forming RGCs, whereas the vLGN and IGL are innervated by non-image-forming RGCs. To explore potential mechanisms regulating class-specific LGN targeting, we sought to identify differentially expressed targeting molecules in these LGN subnuclei. One candidate targeting molecule enriched in the vLGN and IGL during retinogeniculate circuit formation was the extracellular matrix molecule reelin. Anterograde labeling of RGC axons in mutant mice lacking functional reelin (reln(rl/rl)) revealed reduced patterns of vLGN and IGL innervation and misrouted RGC axons in adjacent non-retino-recipient thalamic nuclei. Using genetic reporter mice, we further demonstrated that mistargeted axons were from non-image-forming, intrinsically photosensitive RGCs (ipRGCs). In contrast to mistargeted ipRGC axons, axons arising from image-forming RGCs and layer VI cortical neurons correctly targeted the dLGN in reln(rl/rl) mutants. Together, these data reveal that reelin is essential for the targeting of LGN subnuclei by functionally distinct classes of RGCs.
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298-0709, USA.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Su
authors.forename: Cheryl V
authors.initials: CV
authors.lastname: Haner
authors.forename: Terence E
authors.initials: TE
authors.lastname: Imbery
authors.forename: Justin M
authors.initials: JM
authors.lastname: Brooks
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Morhardt
authors.forename: Karen
authors.initials: K
authors.lastname: Gorse
authors.forename: William
authors.initials: W
authors.lastname: Guido
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fox
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D005829:Geniculate Bodies / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D000091042:Reelin Protein; D012165:Retinal Ganglion Cells / Q000502:physiology*; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases