The overall goal of this research program is to understand how parallel retinofugal pathways are established during development. This proposal focuses on the question of how retinal ganglion cell (RGC) axons select their correct targets and target layers in the brain during development. RGC axon-target and axon-layer matching are both critical aspects of visual circuit organization and yet, very little is known about how they develop in mammals. We propose to study the development of these connections in transgenic mice where specific RGC subtypes express fluorescent proteins and in which specific genes are absent or misexpressed in the retinofugal pathway.
The specific aims of this proposal are to 1) characterize the cellular events that enable RGCs carrying different qualities of visual information to recognize their appropriate targets in the brain, 2) test the hypothesis that the adhesion molecule cadherin-6 controls RGC axon-target matching 3) test the hypothesis that lamina specific targeting of axons from direction selective RGCs to the superior colliculus is mediated by the adhesion molecule cadherin-7. Results from these experiments should lead to new understanding of how mammalian visual circuits are established and inform strategies for maintaining and replenishing visual circuits in response to injury or disease.
The long-term objectives of our research are to understand how central visual pathways are established during development and how those connections can be maintained or replenished in response to diseases or injuries that degrade them. Knowledge gained from these studies will be particularly relevant to diseases of the visual system that impact retinal connections with central targets, such as glaucoma.
|Salay, Lindsey D; Ishiko, Nao; Huberman, Andrew D (2018) A midline thalamic circuit determines reactions to visual threat. Nature 557:183-189|
|Seabrook, Tania A; Dhande, Onkar S; Ishiko, Nao et al. (2017) Strict Independence of Parallel and Poly-synaptic Axon-Target Matching during Visual Reflex Circuit Assembly. Cell Rep 21:3049-3064|
|Seabrook, Tania A; Burbridge, Timothy J; Crair, Michael C et al. (2017) Architecture, Function, and Assembly of the Mouse Visual System. Annu Rev Neurosci 40:499-538|
|Osterhout, Jessica A; Stafford, Benjamin K; Nguyen, Phong L et al. (2015) Contactin-4 mediates axon-target specificity and functional development of the accessory optic system. Neuron 86:985-999|
|Sun, Lu O; Brady, Colleen M; Cahill, Hugh et al. (2015) Functional assembly of accessory optic system circuitry critical for compensatory eye movements. Neuron 86:971-984|
|Tang, Jonathan C Y; Rudolph, Stephanie; Dhande, Onkar S et al. (2015) Cell type-specific manipulation with GFP-dependent Cre recombinase. Nat Neurosci 18:1334-41|
|Dhande, Onkar S; Huberman, Andrew D (2014) Visual circuits: mouse retina no longer a level playing field. Curr Biol 24:R155-6|
|Triplett, Jason W; Wei, Wei; Gonzalez, Cristina et al. (2014) Dendritic and axonal targeting patterns of a genetically-specified class of retinal ganglion cells that participate in image-forming circuits. Neural Dev 9:2|
|Cruz-Martín, Alberto; El-Danaf, Rana N; Osakada, Fumitaka et al. (2014) A dedicated circuit links direction-selective retinal ganglion cells to the primary visual cortex. Nature 507:358-61|
|Osterhout, Jessica A; El-Danaf, Rana N; Nguyen, Phong L et al. (2014) Birthdate and outgrowth timing predict cellular mechanisms of axon target matching in the developing visual pathway. Cell Rep 8:1006-17|
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