Receptors, Notch: A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN repeats in their cytoplasmic domains. The cytoplasmic domain of notch receptors is released upon ligand binding and translocates to the CELL NUCLEUS where it acts as transcription factor.Receptor, Notch2: A notch receptor that plays an important role in CELL DIFFERENTIATION in a variety of cell types. It is the preferentially expressed notch receptor in mature B-LYMPHOCYTES.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Basic Helix-Loop-Helix Transcription Factors: A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.Amyloid Precursor Protein Secretases: Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Precursor T-Cell Lymphoblastic Leukemia-Lymphoma: A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.WingTranscription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Cell Lineage: The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.CADASIL: A familial, cerebral arteriopathy mapped to chromosome 19q12, and characterized by the presence of granular deposits in small CEREBRAL ARTERIES producing ischemic STROKE; PSEUDOBULBAR PALSY; and multiple subcortical infarcts (CEREBRAL INFARCTION). CADASIL is an acronym for Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. CADASIL differs from BINSWANGER DISEASE by the presence of MIGRAINE WITH AURA and usually by the lack of history of arterial HYPERTENSION. (From Bradley et al, Neurology in Clinical Practice, 2000, p1146)Dipeptides: Peptides composed of two amino acid units.Drosophila melanogaster: A species of fruit fly much used in genetics because of the large size of its chromosomes.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Cyclic S-OxidesCell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Body Patterning: The processes occurring in early development that direct morphogenesis. They specify the body plan ensuring that cells will proceed to differentiate, grow, and diversify in size and shape at the correct relative positions. Included are axial patterning, segmentation, compartment specification, limb position, organ boundary patterning, blood vessel patterning, etc.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Embryo, Nonmammalian: The developmental entity of a fertilized egg (ZYGOTE) in animal species other than MAMMALS. For chickens, use CHICK EMBRYO.Animals, Genetically Modified: ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.Somites: Paired, segmented masses of MESENCHYME located on either side of the developing spinal cord (neural tube). Somites derive from PARAXIAL MESODERM and continue to increase in number during ORGANOGENESIS. Somites give rise to SKELETON (sclerotome); MUSCLES (myotome); and DERMIS (dermatome).Dibenzazepines: Compounds with two BENZENE rings fused to AZEPINES.Zebrafish: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.Dementia, Multi-Infarct: Loss of higher cortical functions with retained awareness due to multiple cortical or subcortical CEREBRAL INFARCTION. Memory, judgment, attention span, and impulse control are often impaired, and may be accompanied by PSEUDOBULBAR PALSY; HEMIPARESIS; reflex abnormalities, and other signs of localized neurologic dysfunction. (From Adams et al., Principles of Neurology, 6th ed, p1060)Presenilin-1: Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN1 mutations cause early-onset ALZHEIMER DISEASE type 3 that may occur as early as 30 years of age in humans.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Zebrafish Proteins: Proteins obtained from the ZEBRAFISH. Many of the proteins in this species have been the subject of studies involving basic embryological development (EMBRYOLOGY).Juvenile Hormones: Compounds, either natural or synthetic, which block development of the growing insect.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Genes, Insect: The functional hereditary units of INSECTS.Alagille Syndrome: A multisystem disorder that is characterized by aplasia of intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC), and malformations in the cardiovascular system, the eyes, the vertebral column, and the facies. Major clinical features include JAUNDICE, and congenital heart disease with peripheral PULMONARY STENOSIS. Alagille syndrome may result from heterogeneous gene mutations, including mutations in JAG1 on CHROMOSOME 20 (Type 1) and NOTCH2 on CHROMOSOME 1 (Type 2).Glycosyltransferases: Enzymes that catalyze the transfer of glycosyl groups to an acceptor. Most often another carbohydrate molecule acts as an acceptor, but inorganic phosphate can also act as an acceptor, such as in the case of PHOSPHORYLASES. Some of the enzymes in this group also catalyze hydrolysis, which can be regarded as transfer of a glycosyl group from the donor to water. Subclasses include the HEXOSYLTRANSFERASES; PENTOSYLTRANSFERASES; SIALYLTRANSFERASES; and those transferring other glycosyl groups. EC 2.4.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Morphogenesis: The development of anatomical structures to create the form of a single- or multi-cell organism. Morphogenesis provides form changes of a part, parts, or the whole organism.Nerve Tissue ProteinsCell Line: Established cell cultures that have the potential to propagate indefinitely.Sense Organs: Specialized organs adapted for the reception of stimuli by the NERVOUS SYSTEM.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Insect Proteins: Proteins found in any species of insect.Cell Line, Tumor: A cell line derived from cultured tumor cells.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Presenilins: Integral membrane proteins and essential components of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. Mutations of presenilins lead to presenile ALZHEIMER DISEASE with onset before age 65 years.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Mice, Inbred C57BLNeurogenesis: Formation of NEURONS which involves the differentiation and division of STEM CELLS in which one or both of the daughter cells become neurons.Ubiquitin-Protein Ligases: A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.Wnt1 Protein: A proto-oncogene protein and member of the Wnt family of proteins. It is expressed in the caudal MIDBRAIN and is essential for proper development of the entire mid-/hindbrain region.Mesoderm: The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube.Eye: The organ of sight constituting a pair of globular organs made up of a three-layered roughly spherical structure specialized for receiving and responding to light.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.FucoseMolecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.F-Box Proteins: A family of proteins that share the F-BOX MOTIF and are involved in protein-protein interactions. They play an important role in process of protein ubiquition by associating with a variety of substrates and then associating into SCF UBIQUITIN LIGASE complexes. They are held in the ubiquitin-ligase complex via binding to SKP DOMAIN PROTEINS.ThiadiazolesN-Acetylglucosaminyltransferases: Enzymes that catalyze the transfer of N-acetylglucosamine from a nucleoside diphosphate N-acetylglucosamine to an acceptor molecule which is frequently another carbohydrate. EC 2.4.1.-.
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