Biomedical subjects

D Trisler

Publications and source records attributed to D Trisler.

10 recordsLinked to original sources

PubMed2004

Brain-derived neurotrophic factor (BDNF) gene delivery into the CNS using bone marrow cells as vehicles in mice.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is protective in animal models of neurodegenerative diseases. However, BDNF has a short half-life and its efficacy in the CNS when delivered peripherally is limited due to the blood-brain barrier. In the present study, bone marrow cells were used as vehicles to deliver the BDNF gene into the CNS. Marrow cells obtained from 6 to 8 week-old SJL/J mice were transduced with BDNF expressing pro-virus. RT-PCR analysis revealed that BDNF mRNA was expressed in transduced but not in non-transduced marrow cells. Additionally, virus transduced marrow cells expressed the BDNF protein (296+/-1.2 unit/ml). BDNF-transduced marrow cells were then transplanted into irradiated mice through the tail vein. Three months post-transplantation, significant increases in BDNF as well as glutamic acid decarboxylase (GAD(67)) mRNA were detected in the brains of BDNF transplanted mice compared to untransplanted animals, indicating biological activity of the BDNF transgene. Thus, bone marrow cells can be used as vehicles to deliver the BDNF gene into the brain with implications for the treatment of neurological diseases.

Animals↗

PubMed2002

The myelin basic protein gene is expressed in differentiated blood cell lineages and in hemopoietic progenitors.

Myelin basic proteins (MBP) are major constituents of the myelin sheath of oligodendrocytes and Schwann cells in the central nervous system and the peripheral nervous system, respectively. We previously showed that MBP-related transcripts are present in the bone marrow and the immune system. These mRNAs are transcribed from a region called 0', consisting of three exons, located upstream of the classical MBP exons; these three exons belong to the long MBP gene otherwise called "Golli-MBP." The most abundant of these mRNAs, now called HMBP (hemopoietic MBP), encompasses the sequence encoded by the region 0' plus exon 1 and part of intron 1 of the classic MBP gene. Antisera to recombinant HMBP proteins are immunoreactive with proteins of about 26-28 kDa in brain, thymus, and spleen. This report demonstrates that HMBP proteins are present in the vast majority (>95%) of thymic T cells, which express the corresponding transcripts, as do mature T cells from lymph nodes and spleen. HMBP mRNAs and proteins are also manifest in the majority of spleen B lymphocytes and in B cell lines. In addition to lymphoid cells, HMBP proteins are in all types of myeloid lineage cells, i.e., macrophages, dendritic cells, and granulocytes, as well as in megakaryocytes and erythroblasts. Finally, HMBP proteins are present in CD34+ bone marrow cells, and, furthermore, in highly proliferative cultures, these CD34+ cells express HMBP RNAs and proteins. Thus, MBP gene products are present both in the nervous system and in the entire hemopoietic system.

Animals↗

PubMed1996

Retinal engineering: engrafted neural cell lines locate in appropriate layers.

A major question in central nervous system development, including the neuroretina, is whether migrating cells express cues to find their way and settle at specific locations. We have transplanted quail neuroretinal cell lines QNR/D, a putative amacrine or ganglion cell, and QNR/K2, a putative Müller cell into chicken embryo eyes. Implanted QNR/D cells migrate only to the retinal ganglion and amacrine cell layers and project neurites in the plane of retina; in contrast, QNR/K2 cells migrate through the ganglion and amacrine layers, locate in the inner nuclear layer, and project processes across the retina. These data show that QNR/D and QNR/K2 cell lines represent distinct neural cell types, suggesting that migrating neural cells express distinct address cues. Furthermore, our results raise the possibility that immortalized cell lines can be used for replacement of specific cell types and for the transport of genes to given locations in neuroretina.

Animals↗

PubMed1995

Molecular cloning of TOPAP: a topographically graded protein in the developing chick visual system.

Topographically graded molecules representing position-specific differences among otherwise similar cells are thought to play a role in the patterning of the developing nervous system. In the embryonic chick visual system, a 40 kDa protein, TOPAP, is expressed in a posterior > anterior gradient in the retina and in an inverted anterior > posterior gradient in the optic tectum, the major retinal projection area. Here we report the isolation and nucleotide sequencing of a complementary DNA clone encoding the chick TOPAP protein and demonstrate that the mRNA encoding this coiled-coil integral membrane protein is topographically graded within the retina and is present in a variety of chick tissues.

Amino Acid Sequence↗

PubMed1990

Cell recognition and pattern formation in the developing nervous system.

The topographic map of cell position in the avian retina is conserved and inverted when retinal ganglion neurons synapse with neurons in the optic tectum. Developmental mechanisms based on molecular gradients that specify positional information and pattern formation have been postulated in the establishment of these topographic maps of cells in retina and optic tectum. Two cell surface proteins in retina, TOP(DV) and TOP(AP), are distributed in dorsoventral and anteroposterior topographic gradients, respectively. Corresponding gradients of TOP molecules present in the tectum are inverted with respect to the retinal gradients. These orthogonal gradients of TOP(DV) and TOP(AP) molecules provide a possible Cartesian coordinate system for designation of cell position at all points in the retinotectal map.

Animals↗

PubMed1987

Corresponding spatial gradients of TOP molecules in the developing retina and optic tectum.

The topographic map of cell position in the avian retina is inverted in its projection to the optic tectum. Dorsal retinal ganglion cell axons project to ventral tectum, and ventral retinal ganglion cells project to dorsal tectum. Topographic gradients of toponymic (TOP) cell surface molecules along the dorsoventral axes of retina and tectum also are inverted. TOP molecules are most abundant in dorsal retina and ventral tectum and least abundant in ventral retina and dorsal tectum during the period of initial retinal-tectal interaction. Thus, TOP molecules may be involved in orienting the retinotectal map.

Animals↗

PubMed1987

Synapse formation in retina is influenced by molecules that identify cell position.

Molecules that identify cell type and position in the nervous system were detected by monoclonal antibodies. One molecule, TOP, is distributed in a 35-fold topographic gradient from the dorsoposterior margin to the ventroanterior margin of avian retina. The gradient is present in young embryos, increases with retinal growth, and persists in the adult. TOP molecules are present on most or all cells of retina. The number of TOP molecules detected per cell varies continuously along the axis of the antigen gradient. Thus, TOP can be used to identify position in the plane of retina along that axis. Other antigens that identify cell type and position across the thickness of retina also were detected. Molecules that mark such cellular organization may represent a neuronal recognition system. Antibodies were used to examine the role of markers of cell position in development of the nervous system. Antibody to TOP from hybridoma cells that were injected into in vivo embryo eyes diffused into the retina and bound in a topographic gradient of Ab.TOP complexes. Synapse formation in retina was inhibited in the presence of anti-TOP antibody. This suggests that TOP is involved in synapse formation and that recognition of position by neurons is necessary for normal synapse formation.

Animals↗

PubMed1986

Antibody to a molecular marker of cell position inhibits synapse formation in retina.

A topographic gradient of TOP molecules in retina can be used to identify neuron position. Antibody to TOP from hybridoma cells that were injected into in vivo embryo eyes diffused into the retina and bound in a topographic gradient of [antibody.TOP] ([Ab.TOP]) complexes. Synapse formation in retina was inhibited in the presence of anti-TOP antibody. This suggests that TOP is involved in synapse formation and that recognition of position by neurons is necessary for normal synapse formation.

Animals↗

PubMed1986

Purification of a membrane protein distributed in a topographic gradient in chicken retina.

Antigenic molecules termed TOP, which are distributed in a dorsal greater than ventral concentration gradient in chicken retina, are expressed early in development (by 48 hr after fertilization) in the optic cup of chicken embryos and continue to be expressed in retina thereafter. 35S-labeled-TOP-antibody complexes were purified by protein A-Sepharose column chromatography and subjected to NaDodSO4/polyacrylamide gel electrophoresis and autoradiography. TOP also was purified from dorsal retina by anti-TOP IgG-Affi-Gel 10 affinity column chromatography. In both cases, one major band of protein at Mr approximately 47,000 was obtained. A protein of Mr approximately 47,000 also was purified from chicken embryo brain. Cultured cells dissociated from 8-day chicken embryo retinas accumulated the amount of TOP expected of cells in the intact retina, depending on the position of the cells in the retina. TOP accumulations by cells dissociated from dorsal or ventral retina, mixed in different proportions, and cocultured were additive. These results show that TOP is a protein, that the gradient of TOP is established early in development, and that perpetuation of the gradient does not depend on the continuous presence of an extracellular gradient of diffusable molecules or on maintenance of interactions between cells.

Animals↗

PubMed1985

Monoclonal antibody 18B8 detects gangliosides associated with neuronal differentiation and synapse formation.

Mouse monoclonal antibody 18B8 detects developmentally regulated antigens in chicken retina and brain. The antigens detected by immunofluorescence appear initially on cell bodies in retinas of 6-13 day embryos. In older embryos during synapse formation and in adults, the antigen is localized in discrete laminae within the inner synaptic layer of retina and also is present in the outer synaptic layer and the outer segments of photoreceptor cells. The antigens from retina and brain were purified partially and were shown to be gangliosides of unknown structure that contain at least two sialic acid residues. Gangliosides that are recognized by antibody 18B8 change both qualitatively and quantitatively during neuronal development. These changes were correlated with the spatial and temporal changes in antigen expression detected histochemically.

Animals↗