The long term objectives of this work are to contribute to the elucidation of the structural organization and development of the vertebrate visual system and to clarify the changes that occur in it when it is deprived of its normal visual input. The studies we propose bear directly on the important issue of how the visual system is assembled during embryonic development and on the problems that may result from a variety of developmental abnormalities and from sensory deprivation. In the forthcoming grant period we propose specifically to examine the following: (i) The normal pattern of development of the avian optic tectum and its innervation by the retina, using 3H-thymidine autoradiographic and immunocytochemical techniques, monoclonal antibodies raised against tectal antigens, and a number of experimental manipulations including 180 degree rotation of the alar plate and/or midbrain, and the rerouting of the retinal input to the tectum. (ii) The capacity of the regenerated chick optic tectum for reorganization and morphological plasticity following early unilateral eye removal. (iii) The effects of sensory overloading on the chick tectum and the nucleum of origin of centrifugal fibers to the retina (the so-called isthmo optic nucleus-ION) induced by transplanting supernumerary eyes and producing """"""""compound"""""""" eyes. (iv) The factors involved in the normal elimination of aberrant and exuberant retinal projections in chicks and hamsters, by early manipulations of the retina, optic nerve and optic tectum. (v) The factors responsible for the """"""""guidance"""""""" of centrifugal axons to the chick retina and the fate of ectopic or misplaced centrifugal neurons. (vi) The regulation of naturally-occurring cell death in the retina and ION and especially the role of activity in the maintenance of neurons in these structures.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007025-03
Application #
3263860
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1986-09-30
Project End
1988-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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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