Vesa Kaartinen
University of Michigan, School of Dentistry, Faculty Member
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Research Interests: Developmental Biology, Biology, Immunohistochemistry, Cell Biology, Medicine, and 15 moreExtracellular Matrix, Cell separation, In Situ Hybridization, Biological Sciences, Neural Crest, Mice, Animals, Cell Death, Developmental, Craniofacial, Pseudopodia, Craniofacial Abnormalities, Medical and Health Sciences, Cardiovascular abnormalities, and mouse embryo
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Research Interests: Developmental Biology, Biology, Cell Biology, Medicine, Bone Morphogenetic Proteins, and 15 moreSignal Transduction, Biological Sciences, Mutation, Smad 3, Mice, Animals, Skull, Phenotype, Developmental, Craniosynostosis, Osteoblasts, Smad proteins, Gene Expression Regulation, ACVR, and Medical and Health Sciences
Research Interests: Stem Cells, Biology, Cell Biology, Stem Cell, Medicine, and 15 moreTransgenic Mice, Signal Transduction, Biological Sciences, Cell Differentiation, Articles, Mice, Animals, Polymerase Chain Reaction, Fibroblast Growth Factor, Genotype, Epithelial cells, Incisor, Transforming Growth Factor Beta, Cell Proliferation, and Medical and Health Sciences
Research Interests: Biology, Medicine, Transgenic Mice, Mice, Wnt Signaling, and 13 moreAnimals, Connective tissue, Osteoblast, Glycoproteins, Skeletal Muscle, Osteogenesis, Osteoblasts, Bone and Bones, Biochemistry and cell biology, Sclerostin, Bone mass, Fibrodysplasia Ossificans Progressiva, and Medical biochemistry and metabolomics
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The inner ear develops from a simple epithelium (otic placode) into the complex structures specialized for balance (vestibule) and sound (cochlea) detection. Abnormal vestibular and cochlear development is associated with many birth... more
The inner ear develops from a simple epithelium (otic placode) into the complex structures specialized for balance (vestibule) and sound (cochlea) detection. Abnormal vestibular and cochlear development is associated with many birth defects. During recent years, considerable progress has been made in understanding the molecular bases of these conditions. To determine the biological function of two closely related GTPase activating proteins for the Cdc42/Rac GTPases, Abr and Bcr, we generated a mouse strain deficient in both of these proteins. Double null mutant mice exhibit hyperactivity, persistent circling, and are unable to swim. These phenotypes are typically found in mice with vestibular defects. Indeed, adult double null mutants display abnormal dysmorphic structures of both the saccule and utricle. Moreover, a total loss of otoconia can be seen in the utricle, whereas in the saccule, otoconia are either missing or their number is drastically decreased and they are abnormally large. Interestingly, both the cochlea and semicircular canals are normal and the double null mutant mice are not deaf. These data demonstrate that Abr and Bcr play important complementary roles during vestibular morphogenesis and that a function of Cdc42/RacGAPs and, therefore, that of the small Rho‐related GTPases is critically important for balance and motor coordination. © 2002 Wiley‐Liss, Inc.
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Experiments in cultured cells have implicated the molecular switch Rac in a wide variety of cellular functions. Here we demonstrate that the simultaneous disruption of two negative regulators of Rac, Abr and Bcr, in mice leads to specific... more
Experiments in cultured cells have implicated the molecular switch Rac in a wide variety of cellular functions. Here we demonstrate that the simultaneous disruption of two negative regulators of Rac, Abr and Bcr, in mice leads to specific abnormalities in postnatal cerebellar development. Mutants exhibit granule cell ectopia concomitant with foliation defects. We provide evidence that this phenotype is causally related to functional and structural abnormalities of glial cells. Bergmann glial processes are abnormal and GFAP-positive astroglia were aberrantly present on the pial surface. Older Abr;Bcr-deficient mice show spontaneous mid-brain glial hypertrophy, which can further be markedly enhanced by kainic acid. Double null mutant astroglia are hyper-responsive to stimulation with epidermal growth factor and lipopolysaccharide and exhibit constitutively increased phosphorylation of p38 mitogen-activated protein kinase, which is regulated by Rac. These combined data demonstrate a prominent role for Abr and Bcr in the regulation of glial cell morphology and reactivity, and consequently in granule cell migration during postnatal cerebellar development in mammals.
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Research Interests: Biology, Immunohistochemistry, Cell Biology, Development, Medicine, and 15 moreIn Situ Hybridization, Bone Morphogenetic Proteins, Cell Division, Biological Sciences, Cell Differentiation, Neural Crest, Mutation, Mice, Animals, Heart Development, Cardiovascular system, Genotype, Aorta, Ligands, and Medical and Health Sciences
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Failure of palatogenesis results in cleft palate, one of the most common congenital disabilities in humans. During the final phases of palatogenesis, the protective function of the peridermal cell layer must be eliminated for the medial... more
Failure of palatogenesis results in cleft palate, one of the most common congenital disabilities in humans. During the final phases of palatogenesis, the protective function of the peridermal cell layer must be eliminated for the medial edge epithelia to adhere properly, which is a prerequisite for the successful fusion of the secondary palate. However, a deeper understanding of the role and fate of the periderm in palatal adherence and fusion has been hampered due to a lack of appropriate periderm-specific genetic tools to examine this cell type in vivo. Here we used the cytokeratin-6A (Krt-6a) locus to develop both constitutive ( Krt6ai-Cre) and inducible ( Krt6ai-Cre ERT2) periderm-specific Cre driver mouse lines. These novel lines allowed us to achieve both the spatial and temporal control needed to dissect the periderm fate on a cellular resolution during palatogenesis. Our studies suggest that, already before the opposing palatal shelves contact each other, at least some palatal periderm cells start to gradually lose their squamous periderm-like phenotype and dedifferentiate into cuboidal cells, reminiscent of the basal epithelial cells seen in the palatal midline seam. Moreover, we show that transforming growth factor–β (TGF-β) signaling plays a critical periderm-specific role in palatogenesis. Thirty-three percent of embryos lacking a gene encoding the TGF-β type I receptor ( Tgfbr1) in the periderm display a complete cleft of the secondary palate. Our subsequent experiments demonstrated that Tgfbr1-deficient periderm fails to undergo appropriate dedifferentiation. These studies define the periderm cell fate during palatogenesis and reveal a novel, critical role for TGF-β signaling in periderm dedifferentiation, which is a prerequisite for appropriate palatal epithelial adhesion and fusion.
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New specific methods for laboratory detection of a lysosomal storage disease aspartylglycosaminuria were developed. Aspartylglucosamine, the main metabolite accumulating in the body fluids and tissues in the disease, was measured with... more
New specific methods for laboratory detection of a lysosomal storage disease aspartylglycosaminuria were developed. Aspartylglucosamine, the main metabolite accumulating in the body fluids and tissues in the disease, was measured with high-performance liquid chromatography in urine of aspartylglycosaminuria patients, carriers of the disease and normal controls as well as in amniotic fluid of normal pregnancies and one with the fetus affected by aspartylglycosaminuria. In the diseased patients, the aspartylglucosamine excretion was over 1,000-fold elevated compared to that in the carriers and controls. In the pregnancy with the fetus affected by the disease, the concentration of aspartylglucosamine was only slightly elevated, but lower than that in urine of normal individuals. As a conclusion, the determination of aspartylglucosamine in urine allowed postnatal detection of aspartylglycosaminuria, but in amniotic fluid it was useless in prenatal detection of the disease. The activity of the deficient enzyme in aspartylglycosaminuria, aspartylglycosylaminase, was assayed with a specific gas-chromatographic method. The enzyme activity was shown to lack in plasma, lymphocytes and amniotic fluid of aspartylglycosaminuria patients and the method proved applicable for postnatal and prenatal detection of aspartylglycosaminuria. The enzyme activity in lymphocytes of the carriers fell between those in normal controls and aspartylglycosaminuria patients, and the assay could be used in carrier detection in most of the cases.
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Research Interests: Chemistry, Inorganic Chemistry, Catalysis, Kinetics, Biological Chemistry, and 15 moreMagnetic Resonance Spectroscopy, Medicine, Biological Sciences, Humans, Stereochemistry, CHEMICAL SCIENCES, Amino Acids, Substrate Specificity, Reaction Mechanism, Hydrolysis, Glycosides, Biochemistry and cell biology, Glycopeptides, Medical and Health Sciences, and Medical biochemistry and metabolomics(Magnetic Resonance Spectroscopy, Medicine, Biological Sciences, Humans, Stereochemistry, CHEMICAL SCIENCES, Amino Acids, Substrate Specificity, Reaction Mechanism, Hydrolysis, Glycosides, Biochemistry and cell biology, Glycopeptides, Medical and Health Sciences, and Medical biochemistry and metabolomics)
(Magnetic Resonance Spectroscopy, Medicine, Biological Sciences, Humans, Stereochemistry, CHEMICAL SCIENCES, Amino Acids, Substrate Specificity, Reaction Mechanism, Hydrolysis, Glycosides, Biochemistry and cell biology, Glycopeptides, Medical and Health Sciences, and Medical biochemistry and metabolomics)
Research Interests: Health Sciences, Biology, Adult Stem Cells, Stem Cell, Medicine, and 15 moreBiological Sciences, Bone, Animals, Male, Endochondral Ossification, Muscles, Progenitor Cells, Osteoblast, Skeleton, Phenotype, Joints, Heterotopic Ossification, Mesenchymal Stromal Cells, Fibrodysplasia Ossificans Progressiva, and Medical and Health Sciences
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Research Interests: Developmental Biology, Biology, Cleft Palate, Cell Biology, Apoptosis, and 14 moreMedicine, Signal Transduction, Biological Sciences, Mutation, Mice, Animals, Phenotype, In Vivo, Palate, Epithelium, Transforming Growth Factor Beta, Embryos, Transforming Growth Factor, and Medical and Health Sciences
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Research Interests: Chemistry, Fluorescence Microscopy, Biology, Cell Adhesion, Immunohistochemistry, and 15 moreCell Biology, Biological Chemistry, Adhesion, Cytoskeleton, Biological Sciences, Fibrinogen, Animals, Biological, CHEMICAL SCIENCES, Glutathione Transferase, Detergents, Integrin, CHO cells, Cricetinae, and Medical and Health Sciences
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An aspartylglycosylaminase assay based on high-performance liquid chromatographic analysis of the substrate aspartylglucosamine and product aspartate is described. Aspartylglucosamine and aspartate are derivatized with... more
An aspartylglycosylaminase assay based on high-performance liquid chromatographic analysis of the substrate aspartylglucosamine and product aspartate is described. Aspartylglucosamine and aspartate are derivatized with phenylisothiocyanate and resolved by reverse-phase chromatography. The detection limit for the compounds is 2 pmol. The method can be used for analysis of aspartylglycosylaminase activity in crude cell extracts and tissue samples.
Research Interests: Chemistry, Analytical Chemistry, Chromatography, Medicine, Brain, and 14 morePregnancy, Humans, Female, Amniotic Fluid, D-Aspartic Acid, Lung, High Performance Liquid Chromatography, High Pressure Liquid Chromatography, Analytical Biochemistry, Leukocytes, Biochemistry and cell biology, N-acetylglucosamine, Isothiocyanates, and Reference standards
Research Interests: Cellular Biology, Biology, Cell Biology, Macrophages, Medicine, and 15 moreBiological Sciences, Molecular and cellular biology, Mutation, Mice, Animals, Proteins, Phagocytosis, Arginine, Asparagine, Protein Transport, Cell Membrane, Sequence homology, CHO cells, Cricetinae, and Medical and Health Sciences
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After cessation of lactation, the mammary gland undergoes involution, which is characterized by a massive epithelial cell death and proteolytic degradation of the extracellular matrix. Whereas the expression patterns and also the function... more
After cessation of lactation, the mammary gland undergoes involution, which is characterized by a massive epithelial cell death and proteolytic degradation of the extracellular matrix. Whereas the expression patterns and also the function of TGF-&#35 isoforms during mammary gland branching morphogenesis and lactation are well understood, their expression during postlactational involution and therefore a possible role in this process is poorly known. In this study we show that TGF-&#353 expression is dramatically induced (>fivefold) during mouse mammary gland involution when compared to that of virgin mouse, reaching a maximal expression level at day 4 after weaning. In contrast, other TGF-&#35 isoforms do not display significant increase in expression during involution (TGF-&#351, 1.3-fold and TGF-&#352, &#353 is expressed in the epithelial layer and particularly in myoepithelial cells. A comparison of the kinetics of TGF-&#353 expression to that of programmed cell death and degradation of the basement membrane suggests that TGF-&#353 functions in the remodeling events of the extracellular matrix during the second stage of involution.
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We have previously cloned a segment of a gene, ABR, homologous to the BCR gene, which encodes a protein consisting of three distinct functional domains. In the present study, genomic ABR sequences were used to isolate human ABR cDNAs.... more
We have previously cloned a segment of a gene, ABR, homologous to the BCR gene, which encodes a protein consisting of three distinct functional domains. In the present study, genomic ABR sequences were used to isolate human ABR cDNAs. Surprisingly, the two types of ABR cDNAs identified differed only in their most 5' coding sequences. These are predicted to encode proteins of 93.5 and 92.3 kDa molecular mass. ABR showed a differential expression pattern in various mouse tissues, analogous to that of BCR, and the highest level was found in brain. Similar to BCR, ABR contains a region with homology to DBL, vav, and CDC24, which are likely to or have been shown to encode GTP exchange factors. A domain of ABR with similarity to GAPrho was expressed as a fusion protein in Escherichia coli and was shown to have GAP activity toward rac. Although both ABR and BCR have GAP activity, ABR lacks homology to the serine/threonine kinase domain of BCR. Therefore, ABR is likely to have cellular functions overlapping with but also distinct from those of BCR.