Subject(s)
Cell Differentiation/physiology , Embryonic Development/physiology , Gastrula/metabolism , Germ Layers/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Cadherins/genetics , Cadherins/metabolism , Cell Movement/physiology , Gastrula/cytology , Gene Expression Regulation, Developmental/physiology , Germ Layers/cytology , Humans , Signal Transduction/physiology , Snail Family Transcription Factors , Transcription Factors/metabolism , p38 Mitogen-Activated Protein Kinases/geneticsSubject(s)
Cell Differentiation/physiology , MicroRNAs/physiology , Signal Transduction/physiology , Animals , DNA-Binding Proteins/metabolism , Down-Regulation , Drosophila/embryology , Drosophila/physiology , Drosophila Proteins/metabolism , Drosophila Proteins/physiology , Eye/embryology , Eye Proteins/metabolism , Eye Proteins/physiology , MicroRNAs/genetics , Nerve Tissue Proteins/metabolism , Photoreceptor Cells/embryology , Proto-Oncogene Proteins/metabolism , Repressor Proteins/metabolism , Repressor Proteins/physiology , Stem Cells/metabolism , Stem Cells/physiology , Transcription Factors/metabolismSubject(s)
Cell Transformation, Neoplastic/metabolism , Intestinal Neoplasms/metabolism , Nerve Tissue Proteins/metabolism , Proto-Oncogene Proteins c-jun/metabolism , TCF Transcription Factors/metabolism , Animals , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors , Cell Transformation, Neoplastic/genetics , Genes, APC/physiology , Heterozygote , Intestinal Neoplasms/genetics , Mice , Mutation , Proto-Oncogene Proteins c-jun/genetics , Transcription Factor 4 , Transcription Factors/metabolism , beta Catenin/genetics , beta Catenin/metabolismSubject(s)
Aging/metabolism , DNA Damage/physiology , Mitochondria/metabolism , Oxidative Stress/physiology , Aging/genetics , Aging, Premature/genetics , Aging, Premature/metabolism , Animals , DNA Polymerase gamma , DNA, Mitochondrial/genetics , DNA-Directed DNA Polymerase/genetics , Free Radicals/metabolism , Mice , Mice, Transgenic , Mitochondria/genetics , Mutation/geneticsABSTRACT
Numerous lines of evidence suggest that Notch signaling plays a pivotal role in controlling the production of neurons from progenitor cells. However, most experiments have relied on gain-of-function approaches because perturbation of Notch signaling results in death prior to the onset of neurogenesis. Here, we examine the requirement for Notch signaling in the development of the striatum through the analysis of different single and compound Notch1 conditional and Notch3 null mutants. We find that normal development of the striatum depends on the presence of appropriate Notch signals in progenitors during a critical window of embryonic development. Early removal of Notch1 prior to neurogenesis alters early-born patch neurons but not late-born matrix neurons in the striatum. We further show that the late-born striatal neurons in these mutants are spared as a result of functional compensation by Notch3. Notably, however, the removal of Notch signaling subsequent to cells leaving the germinal zone has no obvious effect on striatal organization and patterning. These results indicate that Notch signaling is required in neural progenitor cells to control cell fate in the striatum, but is dispensable during subsequent phases of neuronal migration and differentiation.
Subject(s)
Corpus Striatum/embryology , Receptor, Notch1/physiology , Receptors, Notch/physiology , Animals , Body Patterning , Corpus Striatum/metabolism , Mice , Morphogenesis , Mutation , Neurons/physiology , Receptor, Notch1/genetics , Receptor, Notch3 , Receptors, Notch/genetics , Signal Transduction , Stem Cells/physiologySubject(s)
DNA-Binding Proteins/immunology , Dendritic Cells/immunology , Fibroblasts/immunology , Interferon Type I/immunology , Receptors, Cell Surface/immunology , Adaptor Proteins, Signal Transducing , Animals , Antigens, Differentiation/immunology , Endosomes/immunology , Fibroblasts/virology , Interferon Regulatory Factor-7 , Mice , Mice, Knockout , Myeloid Differentiation Factor 88 , Receptors, Immunologic/immunology , Toll-Like Receptor 9Subject(s)
Cyclic AMP Response Element-Binding Protein/genetics , Genes, Regulator/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Muscle, Skeletal/embryology , Signal Transduction/genetics , Adenylyl Cyclases/metabolism , Animals , Cyclic AMP-Dependent Protein Kinases/metabolism , Gene Expression Regulation, Developmental/genetics , Mice , Muscle, Skeletal/metabolism , Wnt ProteinsABSTRACT
PTEN is a tumor suppressor protein that dephosphorylates phosphatidylinositol 3,4,5 trisphosphate and antagonizes the phosphatidylinositol-3 kinase signaling pathway. We show here that PTEN can also inhibit cell migration through its C2 domain, independent of its lipid phosphatase activity. This activity depends on the protein phosphatase activity of PTEN and on dephosphorylation at a single residue, threonine(383). The ability of PTEN to control cell migration through its C2 domain is likely to be an important feature of its tumor suppressor activity.
Subject(s)
Cell Movement/physiology , Phosphoric Monoester Hydrolases/chemistry , Phosphoric Monoester Hydrolases/physiology , Tumor Suppressor Proteins/chemistry , Tumor Suppressor Proteins/physiology , Animals , COS Cells , Catalysis , Catalytic Domain , Cell Line, Tumor , Chlorocebus aethiops , Glioma , Humans , Mutation , PTEN Phosphohydrolase , Phosphoprotein Phosphatases/chemistry , Phosphoprotein Phosphatases/metabolism , Phosphoric Monoester Hydrolases/genetics , Phosphoric Monoester Hydrolases/metabolism , Phosphorylation , Phosphothreonine/metabolism , Precipitin Tests , Protein Structure, Tertiary , Recombinant Proteins/pharmacology , Sequence Deletion , Transfection , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolismABSTRACT
Rho GTPases control signal transduction pathways that link cell surface receptors to a variety of intracellular responses. They are best known as regulators of the actin cytoskeleton, but in addition they control cell polarity, gene expression, microtubule dynamics and vesicular trafficking. Through these diverse functions, Rho GTPases influence many aspects of cell behavior. This review will focus specifically on their role in cell migration.
