The long term objectives of this work are to contribute to the elucidation of the normal structural organization and development of the vertebrate visual system, with an emphasis on characterizing the mechanisms that govern the development of connections between the eye and central visual centers. The issues to be addressed by the proposed studies are of broad significance. The experiments will be carried out principally using fetal and postnatal rats, and in chick embryos, combining in vivo and in vitro approaches. As experience has shown, though, the developmental mechanisms identified and characterized in the avian and rodent visual system also operate in the development of the primate visual system. The first of the 4 major aims of this proposal concerns the process of target selection by developing retinal axons.
Aims 2 - 4 characterize the mechanisms employed by retinal axons to develop topographically ordered projections within their principal target structures, the superior colliculus, and its avian homologue, the optic tectum. AlM 1. To characterize in vivo the mode of in growth of rat retinal axons in to the dorsal lateral geniculate nucleus and test in vitro the hypothesis that a target-derived chemoattractant controls the process by which retinal axons select this nucleus for innervation.
AIM 2. To define for the rat retinocollicular projection the temporal sequence of emergence of topographic order from an initially diffuse projection and determine whether topographically aberrant arbors transiently form synaptic contacts.
AIM 3. To characterize in rodents the early targeting of developing retinal axons along the rostral-caudal axis of their primary target, the superior colliculus, and assess using an in vitro assay whether this targeting and subsequent arborization of retinal axons reflect their response to regional-distinctions in molecular cues present on the surfaces of collicular cells.
AIM 4. To evaluate in vivo the growth behavior of developing chick retinal axons to determine their response to putative molecular cues that encode position along the rostral-caudal and medial-lateral axes of their primary target, the optic tectum.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY007025-07
Application #
3263858
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1986-09-30
Project End
1994-11-30
Budget Start
1991-12-06
Budget End
1992-11-30
Support Year
7
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Kim, J H; Youn, B U; Kim, K et al. (2014) Lhx2 regulates bone remodeling in mice by modulating RANKL signaling in osteoclasts. Cell Death Differ 21:1613-21
McLaughlin, Todd; Lim, Yoo-Shick; Santiago, Alicia et al. (2014) Multiple EphB receptors mediate dorsal-ventral retinotopic mapping via similar bi-functional responses to ephrin-B1. Mol Cell Neurosci 63:24-30
Olsen, Olav; Kallop, Dara Y; McLaughlin, Todd et al. (2014) Genetic analysis reveals that amyloid precursor protein and death receptor 6 function in the same pathway to control axonal pruning independent of ?-secretase. J Neurosci 34:6438-47
Simon, David J; Weimer, Robby M; McLaughlin, Todd et al. (2012) A caspase cascade regulating developmental axon degeneration. J Neurosci 32:17540-53
Feldheim, David A; O'Leary, Dennis D M (2010) Visual map development: bidirectional signaling, bifunctional guidance molecules, and competition. Cold Spring Harb Perspect Biol 2:a001768
Nikolaev, Anatoly; McLaughlin, Todd; O'Leary, Dennis D M et al. (2009) APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457:981-9
Lim, Yoo-Shick; McLaughlin, Todd; Sung, Tsung-Chang et al. (2008) p75(NTR) mediates ephrin-A reverse signaling required for axon repulsion and mapping. Neuron 59:746-58
Hoopfer, Eric D; McLaughlin, Todd; Watts, Ryan J et al. (2006) Wlds protection distinguishes axon degeneration following injury from naturally occurring developmental pruning. Neuron 50:883-95
McLaughlin, Todd; O'Leary, Dennis D M (2005) Molecular gradients and development of retinotopic maps. Annu Rev Neurosci 28:327-55
O'Leary, Dennis D M; McLaughlin, Todd (2005) Mechanisms of retinotopic map development: Ephs, ephrins, and spontaneous correlated retinal activity. Prog Brain Res 147:43-65

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