Abstract
Neural circuitry formation depends on the molecular control of axonal projection during development. By screening with fluorophore-assisted light inactivation in the developing mouse brain, we identified cartilage acidic protein-1B as a key molecule for lateral olfactory tract (LOT) formation and named it LOT usher substance (LOTUS). We further identified Nogo receptor-1 (NgR1) as a LOTUS-binding protein. NgR1 is a receptor of myelin-derived axon growth inhibitors, such as Nogo, which prevent neural regeneration in the adult. LOTUS suppressed Nogo-NgR1 binding and Nogo-induced growth cone collapse. A defasciculated LOT was present in lotus-deficient mice but not in mice lacking both lotus- and ngr1. These findings suggest that endogenous antagonism of NgR1 by LOTUS is crucial for normal LOT formation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Axons / physiology*
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Binding Sites
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Calcium-Binding Proteins / chemistry
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism*
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Cell Line
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Cells, Cultured
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GPI-Linked Proteins / genetics
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GPI-Linked Proteins / metabolism
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Growth Cones / metabolism
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Humans
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Immunohistochemistry
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Ligands
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Mice
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Mice, Inbred ICR
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Myelin Proteins / genetics
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Myelin Proteins / metabolism*
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Nogo Proteins
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Nogo Receptor 1
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Olfactory Pathways / cytology*
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Olfactory Pathways / growth & development*
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Olfactory Pathways / metabolism
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Prosencephalon / embryology
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Prosencephalon / metabolism
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Protein Binding
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism*
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Signal Transduction
Substances
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Calcium-Binding Proteins
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Crtac1 protein, mouse
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GPI-Linked Proteins
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Ligands
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Myelin Proteins
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Nogo Proteins
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Nogo Receptor 1
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RTN4 protein, human
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Receptors, Cell Surface
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Rtn4 protein, mouse
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Rtn4r protein, mouse