Biomedical subjects

Richard P Tucker

Publications and source records attributed to Richard P Tucker.

12 recordsLinked to original sources

PubMed2006

Teneurins: transmembrane proteins with fundamental roles in development.

Teneurins are a novel family of transmembrane proteins expressed during pattern formation and morphogenesis. Originally discovered as ten-m and ten-a in Drosophila, four vertebrate teneurins as well as a Caenorhabditis elegans homologue were identified. The conserved domain architecture of teneurins includes an intracellular domain containing polyproline motifs. The long extracellular domain consists of eight EGF-like repeats, a region of conserved cysteines and unique YD-repeats. Vertebrate teneurins are most prominently expressed in the developing central nervous system, but are also expressed in developing limbs. In C. elegans, RNAi experiments and studies of mutants reveal that teneurins are required during fundamental developmental processes like cell migration and axon pathfinding. Cell culture experiments suggest that the intracellular domain of teneurins translocates to the nucleus following release from the membrane by proteolytic processing. Interestingly, the human teneurin-1 gene is located on the X-chromosome in a region where several families with X-linked mental retardation are mapped.

Alternative Splicing↗

PubMed2006

Avian tenascin-W: expression in smooth muscle and bone, and effects on calvarial cell spreading and adhesion in vitro.

Tenascins are glycoproteins found primarily in the embryonic extracellular matrix. Here we have characterized the fourth and final member of the tenascin family in birds: tenascin-W. Avian tenascin-W has 3.5 epidermal growth factor-like repeats, 6 fibronectin type III domains, and a C-terminal fibrinogen-related domain. Immunohistochemistry reveals that avian tenascin-W is expressed transiently in developing smooth muscle, tendons, and ligaments, but the primary site of tenascin-W expression during development is in the extracellular matrix of bone and the cellular periosteum. In bony matrix, tenascin-W-coated fibrils partly overlap with fibrils that contain tenascin-C. The anti-tenascin-W also labels fibrils in cultures of osteogenic embryonic chicken calvarial cells. Primary calvarial cells cultured on purified tenascin-W become rounded, and fewer of these cells spread on fibronectin when tenascin-W is added to the medium when compared with calvarial cells cultured on fibronectin alone. Moreover, tenascin-W reduces the adhesion of calvarial cells to collagen type I in a shear force assay. We conclude that tenascin-W is likely to play a phylogenetically conserved role in developing bone and that it shares some of the basic anti-adhesive and matrix modulatory properties as tenascin-C.

Amino Acid Sequence↗

PubMed2005

Tenascin-W is found in malignant mammary tumors, promotes alpha8 integrin-dependent motility and requires p38MAPK activity for BMP-2 and TNF-alpha induced expression in vitro.

Tenascins represent a family of extracellular matrix glycoproteins with distinctive expression patterns. Here we have analyzed the most recently described member, tenascin-W, in breast cancer. Mammary tumors isolated from transgenic mice expressing hormone-induced oncogenes reveal tenascin-W in the stroma around lesions with a high likelihood of metastasis. The presence of tenascin-W was correlated with the expression of its putative receptor, alpha8 integrin. HC11 cells derived from normal mammary epithelium do not express alpha8 integrin and fail to cross tenascin-W-coated filters. However, 4T1 mammary carcinoma cells do express alpha8 integrin and their migration is stimulated by tenascin-W. The expression of tenascin-W is induced by BMP-2 but not by TGF-beta1, though the latter is a potent inducer of tenascin-C. The expression of tenascin-W is dependent on p38MAPK and JNK signaling pathways. Since preinflammatory cytokines also act through p38MAPK and JNK signaling pathways, the possible role of TNF-alpha in tenascin-W expression was also examined. TNF-alpha induced the expression of both tenascin-W and tenascin-C, and this induction was p38MAPK- and cyclooxygenase-dependent. Our results show that tenascin-W may be a useful diagnostic marker for breast malignancies, and that the induction of tenascin-W in the tumor stroma may contribute to the invasive behavior of tumor cells.

Bone Morphogenetic Protein 2↗

PubMed2005

Medical gross anatomy as a predictor of performance on the USMLE Step 1.

Traditional predictors of medical school performance, such as Medical College Admission Test (MCAT) scores and grade point averages, are often used during the admissions process to help identify the prospective students who are most likely to complete the basic science portion of the curriculum successfully. Here we analyzed the admissions files and student records of 285 first-year medical students who matriculated at the University of California at Davis School of Medicine between 1999 and 2001 to determine if performance in medical gross anatomy is a similar, if not better, predictor of performance on the United States Medical Licensing Examination (USMLE) Step 1 than traditional predictors used by medical school admissions committees. Though MCAT scores and grade point averages were correlated with scores on the USMLE Step 1, only the score on the biological science section of the MCAT was significantly correlated with passing the licensing examination. In contrast, class rank in medical gross anatomy and the score on a gross anatomy comprehensive final examination were correlated both with scores on the USMLE Step 1 and passing the examination. Our results indicate that medical schools should consider performance in medical gross anatomy just as much, if not more, than traditional predictors of medical school performance when trying to identify students who may need more time or tutoring to pass the licensing examination.

Anatomy↗

PubMed2005

Undergraduate coursework in anatomy as a predictor of performance: comparison between students taking a medical gross anatomy course of average length and a course shortened by curriculum reform.

The performance of students taking medical gross anatomy at the University of California at Davis during a 4-year period (1999-2002) was correlated with prior undergraduate anatomy coursework. Significant correlations were observed between class rank in medical anatomy and taking any undergraduate anatomy as well as the total number of undergraduate anatomy units (P<0.01). Taking human gross anatomy and an anatomy laboratory course were significantly correlated with medical anatomy class rank (P<0.01) as were grades in human anatomy, comparative vertebrate anatomy and anatomy laboratory courses (P<0.05). The medical anatomy course offered in 1999-2000 was 172 hr long, and the course offered in 2001-2002 was 135 hr long, with most of the difference made by decreasing lecture time while sparing the dissection laboratory. The reduction in course length was the consequence of a curriculum-wide cap in weekly contact hours. In the 172-hr medical anatomy course there were significant correlations between the students who took undergraduate anatomy and both class rank and the score on the final examination (P<0.01). These correlations did not exist for the 135-hr course. This may be explained by previous anatomy experiences helping students learn from lecture more than from dissection laboratory, as well as the extra study time available to students in the reformed medical curriculum. Pre-medical students and health science advisors need to consider that the benefits of taking anatomy as an undergraduate may be dependent on the configuration of a medical school's curriculum.

Adult↗

PubMed2004

The thrombospondin type 1 repeat superfamily.

The TSR superfamily is a diverse family of extracellular matrix and transmembrane proteins, many of which have functions related to regulating matrix organization, cell-cell interactions and cell guidance. This review samples some of the contemporary literature regarding TSR superfamily members (e.g. F-spondin, UNC-5, ADAMTS, papilin, and TRAP) where specific functions are assigned to the TSR domains. Combining these observations with the published crystal structure of the TSRs of thrombospondin-1 may hold a key to the development of therapeutic agents for fighting parasitic infection and tumor growth.

Amino Acid Sequence↗

PubMed2004

Connective tissues: signalling by tenascins.

Different connective tissue cells secrete different types of tenascins. These glycoproteins contribute to extracellular matrix (ECM) structure and influence the physiology of the cells in contact with the tenascin containing environment. Tenascin-C expression is regulated by mechanical stress. It shows highest expression in connective tissue surrounding tumors, in wounds and in inflamed tissues where it may regulate cell morphology, growth, and migration by activating diverse intracellular signalling pathways. Thus, integrin and syndecan signalling is influenced by tenascin-C and the levels and/or activies of several proteins involved in intracellular signalling pathways are regulated by its presence. Tenascin-X is important for the proper deposition of collagen fibers in dermis and patients with a tenascin-X deficiency suffer from Ehlers Danlos syndrome. Tenascin-R (and -C) is prominent in the nervous system and has an impact on neurite outgrowth and synaptic functions, and tenascin-W is found in the extracellular matrix of bone, muscle, and kidney. Cell facts:bone: osteoblasts produce tenascin-C, -W cartilage: perichondrial cells produce tenascin-C tendon: fibroblasts produce tenascin-C smooth muscle cells produce tenascin-W, -C skeletal muscle: endo-, peri-, and epimysial fibroblasts produce tenascin-X dermal fibroblasts produce tenascin-X tumors: stromal fibroblasts produce tenascin-C wounds: fibroblasts produce tenascin-C nervous system: glial cells produce tenascin-R, -C, -X.

Cell Shape↗

PubMed2004

Antisense knockdown of the beta1 integrin subunit in the chicken embryo results in abnormal neural crest cell development.

Neural crest cells escape the neural tube by undergoing an epithelial to mesenchymal transition (EMT). This is followed by extensive migration along specific pathways that are lined with extracellular matrix (ECM). In this study, we have examined the roles of matrix receptors containing beta1 integrin subunits in neural crest cell morphogenesis using antisense morpholino oligos electroporated in ovo into avian neural crest cell precursors. Our results show that reduced levels of expression of beta1 integrin subunits in the dorsal neural tube results in an abnormal epithelial to mesenchymal transition. In approximately half of the experimental embryos, however, some neural crest cells filled with beta1 antisense are able to escape the neural tube and migrate ventrally, indicating that grossly normal migration of trunk neural crest cells can take place after beta1 integrin expression is reduced. This study shows the potential of this novel method for investigating the roles of genes that are required for the survival of early mouse embryos in later development events.

Animals↗

PubMed2004

Neural crest cells: a model for invasive behavior.

Neural crest cells are the embryonic precursors of the neurons and glia of the peripheral nervous system, pigment cells, and connective tissue in the face, neck and heart. They are induced near the junction of the neural plate and embryonic ectoderm and undergo an epithelial to mesenchymal transition (EMT). Neural crest cells then display invasive behavior and migrate into the surrounding tissues along specific pathways. Neural crest cells are amenable to study in tissue culture, and the molecules that regulate their development can be studied in vivo with antisense techniques as well as with the expression of gain and loss-of-function constructs. Mutations in factors that regulate neural crest cell survival or differentiation can lead to cell death or the premature cessation of their migration, resulting in craniofacial abnormalities, pigmentation defects and the absence of enteric neurons. This paper reviews recent advances in our understanding of neural crest cell induction and migration, emphasizing both avian and amphibian models. Cell facts: The embryonic progenitors of pigment cells, the neurons and glia of the peripheral nervous system, as well as connective tissue in the face, neck and heart. Induced to form at the boundary of the neuroepithelium and embryonic ectoderm. Expression of the transcription factors Snail, Slug and FoxD3 leads to delamination from the neural tube. Invasive motility not unlike that of tumor cells can be studied in vitro. Express proteases, distinctive cell surface receptors and glycoproteins to acquire an invasive phenotype. Mutations of transcription factors expressed by the neural crest or in other factors that inhibit their premature differentiation can lead to survival and migration-associated birth defects.

Animals↗

PubMed2003

Methods for introducing morpholinos into the chicken embryo.

The use of antisense morpholino oligos to inhibit the translation of a target transcript has been applied recently to studies of the chicken embryo. In contrast to other developmental systems such as in frog, sea urchin, and zebrafish that permit the direct microinjection of morpholinos into a blastomere, square pulse electroporation is used to introduce fluorescently tagged morpholinos into specific populations of chick embryo cells in ovo. This article reviews the methods that have proven successful, the types of controls that are necessary when performing knockdowns of gene expression in the chick embryo, and discusses the limitations of the current technique, as well as directions for further research.

Animals↗

PubMed2002

Detection of glycine receptor/Cl- channel beta subunit transcripts in mouse testis.

The sperm glycine receptor/Cl- channel (GlyR) is important to the initiation of the mammalian sperm acrosome reaction by the egg zona pellucida, but its presence in spermatogenic cells has not been demonstrated. Reverse transcriptase-polymerase chain reaction studies confirmed that GlyR beta subunit transcripts similar to those of the neuronal GlyR beta subunit are present in the testis of Swiss Webster mice. In situ hybridisation analysis demonstrated that GlyR beta subunit mRNAs were expressed within the germ cells of seminiferous tubules in those mice.

Animals↗

PubMed2002

Teneurin 2 is expressed by the neurons of the thalamofugal visual system in situ and promotes homophilic cell-cell adhesion in vitro.

The transmembrane glycoprotein teneurin 2 is expressed by neurons in the developing avian thalamofugal visual system at periods that correspond with target recognition and synaptogenesis. Partial and full-length teneurin 2 constructs were expressed in cell lines in vitro. Expression of the cytoplasmic domain is required for the induction of filopodia, the transport of teneurin 2 into neurites and the co-localization of teneurin 2 with the cortical actin cytoskeleton. In addition, expression of the extracellular domain of teneurin 2 by HT1080 cells induced cell aggregation, and the extracellular domain of teneurin 2 became concentrated at sites of cell-cell contact in neuroblastoma cells. These observations indicate that the homophilic binding of teneurin 2 may play a role in the development of specific neuronal circuits in the developing visual system.

Animals↗