Biomedical subjects

Harris Morrison

Publications and source records attributed to Harris Morrison.

5 recordsLinked to original sources

PubMed2006

Tomographic molecular imaging and 3D quantification within adult mouse organs.

A convenient technology to quantify three-dimensional (3D) morphological features would have widespread applications in biomedical research. Based on combined improvements in sample preparation, tomographic imaging and computational processing, we present a procedure for high-resolution 3D quantification of structures within intact adult mouse organs. Using the nonobese diabetic (NOD) mouse model, we demonstrate a correlation between total islet beta-cell volume and the onset of type-1 diabetes.

Animals↗

PubMed2006

Visualizing plant development and gene expression in three dimensions using optical projection tomography.

A deeper understanding of the mechanisms that underlie plant growth and development requires quantitative data on three-dimensional (3D) morphology and gene activity at a variety of stages and scales. To address this, we have explored the use of optical projection tomography (OPT) as a method for capturing 3D data from plant specimens. We show that OPT can be conveniently applied to a wide variety of plant material at a range of scales, including seedlings, leaves, flowers, roots, seeds, embryos, and meristems. At the highest resolution, large individual cells can be seen in the context of the surrounding plant structure. For naturally semitransparent structures, such as roots, live 3D imaging using OPT is also possible. 3D domains of gene expression can be visualized using either marker genes, such as beta-glucuronidase, or more directly by whole-mount in situ hybridization. We also describe tools and software that allow the 3D data to be readily quantified and visualized interactively in different ways.

Flowers↗

PubMed2005

Foxg1 is required for specification of ventral telencephalon and region-specific regulation of dorsal telencephalic precursor proliferation and apoptosis.

Null mutation of the Foxg1 gene causes hypoplasia of the mouse telencephalon and loss of ventral telencephalic structures. We show that a crucial early requirement for Foxg1 is in the induction of ventral cell fate in the telencephalon. To study later proliferative defects, we have adapted an iododeoxyuridine and bromodeoxyuridine double labeling protocol for use in the developing embryo, which allows estimation of cell cycle kinetics in a single specimen. This technique is used to demonstrate that the cell cycle is prematurely lengthened in the Foxg1-null telencephalon. These defects are first apparent at embryonic day 10.5 (E10.5) and are most severe in the rostral telencephalon. We show that apoptosis is also reduced in the same rostral domain. These defects correspond temporally and spatially with a dramatic reduction in expression of the potent signaling molecule Fgf8. We also show that in the absence of Foxg1 an excess of neurons is produced from E11.5, depleting the progenitor pool and limiting the growth of the Foxg1(-/-) telencephalon. The increase in neurogenic division coincides with an increase in BMP signaling, as detected by immunohistochemistry for phosphorylated smad-1, -5, and -8. This study reinforces Foxg1's position as a major regulator of telencephalic neurogenesis and supports the idea that Foxg1 controls precursor proliferation via regulation of Fgf signaling and differentiation via regulation of Bmp signaling.

Animals↗

PubMed2002

Heterochromatin, HP1 and methylation at lysine 9 of histone H3 in animals.

We show that methylated lysine 9 of histone H3 (Me9H3) is a marker of heterochromatin in divergent animal species. It localises to both constitutive and facultative heterochromatin and replicates late in S-phase of the cell cycle. Significantly, Me9H3 is enriched in the inactive mammalian X chromosome (Xi) in female cells, as well as in the XY body during meiosis in the male, and forms a G-band pattern along the arms of the autosomes. Me9H3 is a constituent of imprinted chromosomes that are repressed. The paternal and maternal pronuclei in one-cell mouse embryos show a striking non-equivalence in Me9H3: the paternal pronucleus contains no immunocytologically detectable Me9H3. The levels of Me9H3 on the parental chromosomes only become equivalent after the two-cell stage. Finally, we provide evidence that Me9H3 is neither necessary nor sufficient for localisation of heterochromatin protein 1 (HP1) to chromosomal DNA.

Animals↗

PubMed2002

Allele-specific underacetylation of histone H4 downstream from promoters is associated with X-inactivation in human cells.

We have used a novel approach to investigate the histone H4 acetylation status at X-inactivated genes compared with their active counterparts. Immunoprecipitation with a sheep antibody that preferentially binds multiply-acetylated H4 isoforms was used to select hyperacetylated chromatin from a human female lymphoblastoid cell line exhibiting non-random X-inactivation as a result of an X/autosome translocation. The distribution of active and inactive gene sequences between the immunoprecipitated and bulk chromatin was compared at four X-linked loci containing intragenic polymorphic microsatellite repeats to allow identification of individual alleles by polymerase chain reaction. We find that DNA sequences corresponding to transcriptionally silent alleles are consistently under-represented in the hyperacetylated fraction. As the microsatellite repeat sequences used to identify alleles range in distance from 6.5 kb to 25 kb downstream of promoters, we conclude that differential H4 acetylation of active and silent chromatin is not confined to regions involved in the initiation of transcription, contrary to previous reports.

Acetylation↗