Biomedical subjects

Seong-Seng Tan

Publications and source records attributed to Seong-Seng Tan.

26 records · Page 2Linked to original sources

PubMed2002

Analysis of cell lineage relationships in taste buds.

Taste buds are a heterogeneous population of cells exhibiting diverse morphological and biochemical characteristics. Because taste buds arise from multiple progenitors, the different types of taste cells may represent distinct lineages. The present study was undertaken to determine the following: (1) how many progenitors contribute to a taste bud, and (2) whether the specific subpopulation of serotonin-immunoreactive (IR) taste cells are related by lineage to a restricted set of progenitor cells. These questions were addressed using cell lineage analysis of taste buds from H253 X-inactivation mosaic mice. After random X-inactivation of the lacZ transgene, the tongue of hemizygous female mice displays discrete patches of epithelial cells, which are either beta-galactosidase (beta-gal) positive or beta-gal negative. By analyzing the proportion of the two differently stained cell populations in taste buds located at the boundary between positive and negative epithelial patches, we can determine the minimum number of progenitors that may contribute to the formation of a taste bud. The presence of taste buds containing only 6-12% labeled cells indicates that at least eight progenitors contribute to an average taste bud of 55 cells, assuming progenitors contribute equally to the cell population. Cell lineage analysis of serotonin-IR taste cells in such mixed taste buds suggests that this subpopulation likely arises from only one to two progenitors and often is related by lineage. Thus, at least some of the cell types in a taste bud represent distinct lineages of cells and are not merely phenotypic stages as a cell progresses from a young to a mature state.

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PubMed2002

Clonal architecture of the mouse hippocampus.

Experimental mouse chimeras have proven useful in analyzing the cell lineages of various tissues. Here we use experimental mouse chimeras to study cell lineage of the hippocampus. We examined clonal architecture and lineage relationships of the hippocampal pyramidal cells, dentate granule cells, and GABAergic interneurons. We quantitatively analyzed like-genotype cohorts of these neuronal populations in the hippocampus of the most highly skewed chimeras to provide estimates of the size of the progenitor pool that gives rise to these neuronal groups. We also compared the percentage chimerism across various brain structures to gain insights into the origins of the hippocampus relative to other neighboring regions of the brain. Our qualitative analyses demonstrate that like-genotype cohorts of pyramidal cells are aligned in radial arrays across the pyramidal cell layer, whereas like-genotype cohorts in the C-shaped dentate gyrus colonize either the outer shell or inner core of the granule cell layer in a symmetrical manner. Clonally related populations of GABAergic interneurons are dispersed throughout the hippocampus and originate from progenitors that are separate from either pyramidal or granule cells. Granule and pyramidal cells, however, are closely linked in their lineages. Our quantitative analyses yielded estimates of the size of the progenitor pools that establish the pyramidal, granule, and GABAergic interneuronal populations as consisting of 7000, 400, and 40 progenitors, respectively, for each side of the hippocampus. Last, we found that the hippocampal pyramidal and granule cells share a lineage with cortical and diencephalic cells, pointing toward a common lineage that crosses the di-telencephalic boundaries.

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PubMed2002

Cellular dispersion patterns and phenotypes in the developing mouse superior colliculus.

The mammalian superior colliculus is structurally and functionally divided into two entities: superficial visual and deep multimodal motor. To discover the role, if any, of developmental processes in establishing separate tectal compartments, we have used highly unbalanced mouse chimaeras to mark cell dispersion pathways and trace cell lineages. Two forms of cell dispersion were detected: radial and tangential. Neither radial nor tangential forms of cell dispersion were found to exist on their own in any group of labeled cells. Radial cell dispersion was the predominant form of cell movement from the germinal zones and primarily associated with the differentiation of glutamatergic neurons. In contrast, tangential cell dispersion involved a minority of tectal cells, concentrated chiefly in the superficial layers and often associated with the upper aspects of radial columns. More scattered cells expressed gamma-aminobutyric acid (GABA) compared to columnar cells. Taken together, these results indicate separate developmental constraints for the development of glutamatergic and GABAergic neurons in the superior colliculus.

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PubMed2002

Clonal analysis of patterns of growth, stem cell activity, and cell movement during the development and maintenance of the murine corneal epithelium.

Patterns of growth and cell movement in the developing and adult corneal epithelium were investigated by analysing clonal patches of LacZ-expressing cells in chimeric and X-inactivation mosaic mice. It was found that cell proliferation throughout the basal corneal epithelium during embryogenesis and early postnatal life creates a disordered mosaic pattern of LacZ(+) clones that contrasts with patterns of proliferation and striping produced during the later embryonic stages of retinal pigmented epithelium development. The early mosaic pattern in the corneal epithelium is replaced in the first 12 postnatal weeks by an ordered pattern of radial stripes or sectors that reflects migration without mixing of the progeny of clones of limbal stem cells. In contrast to previous assumptions, it was found that maturation of the activity of limbal stem cells and the pattern of migration of their progeny are delayed for several weeks postnatally. No evidence was found for immigration of the progeny of stem cells until the 5th postnatal week. There are approximately 100 clones of limbal stem cells initially, and clones are lost during postnatal life. Our studies provide a new assay for limbal and corneal defects in mutant mice.

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PubMed2002

Slit promotes branching and elongation of neurites of interneurons but not projection neurons from the developing telencephalon.

Proper neuronal migration and establishment of circuitry are key processes for laying down the functional network of cortical neurons. A variety of environmental guidance cues, attractive or repulsive, have been shown to guide cell migration and axon arborization. One of these, Slit, appears to possess contrarian properties; it can either inhibit axon outgrowth or promote branching and elongation. The object of the present study was to assess the effect of Slit on MGE and neocortical neurons in culture and in the developing ventricle. When cocultured with a Slit source, E13.5 MGE explants displayed inhibited neurite outgrowth while GABA neuron dispersion away from Slit was increased. Similar inhibition of neurite outgrowth was seen in dissociated cells from E13.5 MGE, these cells were identified to be interneurons based upon their GABA staining. In contrast, E13.5 interneurons, after culture for another 5 days, were responsive to Slit by neurite branching and elongation. Projection neurons, identified by lack of GABA staining, did not respond to Slit, either by branching or elongation. Furthermore, GABA interneurons but not pyramidal neurons, appeared to avoid neocortical areas close to an implanted source of Slit in the ventricular wall. These results lead us to suggest that interneurons but not projection neurons are responsive to the chemorepellant effect of Slit. However, more mature interneurons appear to respond to Slit by neurite arborization. These results demonstrate a selective response to Slit by GABAergic neurons during neocortical development.

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PubMed2002

Region-specific expression of the helix-loop-helix gene BETA3 in developing and adult brains.

Members of the basic helix-loop-helix (bHLH) transcription factor family are crucial regulators of neuronal cell generation and cell fate. A number of bHLH genes are expressed in the developing cerebral cortex, including MASH-1, neurogenin2 and NeuroD implying the existence of a regulatory and possibly redundant network of family members. BETA3 is a novel member originally cloned from pancreatic cells but we report here highly restricted expression patterns in developing forebrain structures that are highly stage-specific. We show that BETA3 mRNA is found in both neocortex and archicortex, mainly in cells that have reached their migratory destinations but is largely absent from proliferative zones. These expression data would suggest that BETA3 function is linked to the establishment rather than the initiation of neuronal fates.

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PubMed2002

Localized expression of the seizure-related gene SEZ-6 in developing and adult forebrains.

Despite its initial identification in neurons exposed to the seizure-inducing drug pentylentetrazole (PTZ), the function of the seizure-related gene SEZ-6 remains obscure. Expression analysis indicates specific expression in the adult brain and testis, and the structure of the predicted protein suggests putative roles in cell-cell recognition and signalling. We report here that type I SEZ-6 mRNA is strongly expressed in highly specific regions in the developing forebrain. Specifically, the pattern of SEZ-6 expression is closely tied with the emergence of the neocortical layers and hippocampus, and implies a forebrain-specific role for this gene during development. In the adult hippocampus, SEZ-6 appears to be a CA1-specific regional marker.

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PubMed2002

Global gene expression analysis of developing neocortex using SAGE.

The mammalian brain is estimated to contain about a hundred billion neurons, making it the most complex biological structure on earth. Trying to understand the assembly and function of this elaborate organ is a formidable task. Yet the information to build a brain is encoded by no more than a subset of the 80,000 genes present in the genome, a more manageable number. This review describes the use of SAGE technology (Serial Analysis of Gene Expression) to decode the genetic repertoire of genes that are differentially expressed in time and in space during development of the neocortex, the part of the mammalian brain responsible for complex traits. We demonstrate that SAGE is not only powerful for generating comprehensive molecular portraits from the developing cortex but can also assist in discovering new genes.

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