Abstract
Nuclear movement is critical during neurogenesis and neuronal migration, which are fundamental for mammalian brain development. Although dynein, Lis1, and other cytoplasmic proteins are known for their roles in connecting microtubules to the nucleus during interkinetic nuclear migration (INM) and nucleokinesis, the factors connecting dynein/Lis1 to the nuclear envelope (NE) remain to be determined. We report here that the SUN-domain proteins SUN1 and SUN2 and the KASH-domain proteins Syne-1/Nesprin-1 and Syne-2/Nesprin-2 play critical roles in neurogenesis and neuronal migration in mice. We show that SUN1 and SUN2 redundantly form complexes with Syne-2 to mediate the centrosome-nucleus coupling during both INM and radial neuronal migration in the cerebral cortex. Syne-2 is connected to the centrosome through interactions with both dynein/dynactin and kinesin complexes. Syne-2 mutants also display severe defects in learning and memory. These results fill an important gap in our understanding of the mechanism of nuclear movement during brain development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Behavior, Animal / physiology
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Brain / cytology
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Bromodeoxyuridine / metabolism
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Cell Movement / genetics
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Cell Movement / physiology
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Cell Nucleus / metabolism
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Cell Proliferation
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Cells, Cultured
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Centrosome / metabolism*
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Cytoskeletal Proteins
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Dyneins / metabolism
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Electroporation / methods
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Exploratory Behavior / physiology
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Female
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Membrane Proteins / deficiency
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Membrane Proteins / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Microtubule-Associated Proteins / deficiency
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Microtubule-Associated Proteins / metabolism*
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Nerve Tissue Proteins / deficiency
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Nerve Tissue Proteins / metabolism*
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Neurogenesis / genetics
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Neurogenesis / physiology*
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Neurons / cytology*
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Neurons / ultrastructure
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Nuclear Proteins / deficiency
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Nuclear Proteins / metabolism*
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Pregnancy
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Protein Interaction Mapping / methods
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Protein Structure, Tertiary / genetics
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Protein Transport / physiology
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Telomere-Binding Proteins / deficiency
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Telomere-Binding Proteins / metabolism*
Substances
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Cytoskeletal Proteins
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Membrane Proteins
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Microtubule-Associated Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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SUN1 protein, mouse
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Sun2 protein, mouse
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Syne1 protein, mouse
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Syne2 protein, mouse
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Telomere-Binding Proteins
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Dyneins
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Bromodeoxyuridine