Biomedical subjects

Marc Kirschner

Publications and source records attributed to Marc Kirschner.

4 recordsLinked to original sources

PubMed2003

Anteroposterior patterning in hemichordates and the origins of the chordate nervous system.

The chordate central nervous system has been hypothesized to originate from either a dorsal centralized, or a ventral centralized, or a noncentralized nervous system of a deuterostome ancestor. In an effort to resolve these issues, we examined the hemichordate Saccoglossus kowalevskii and studied the expression of orthologs of genes that are involved in patterning the chordate central nervous system. All 22 orthologs studied are expressed in the ectoderm in an anteroposterior arrangement nearly identical to that found in chordates. Domain topography is conserved between hemichordates and chordates despite the fact that hemichordates have a diffuse nerve net, whereas chordates have a centralized system. We propose that the deuterostome ancestor may have had a diffuse nervous system, which was later centralized during the evolution of the chordate lineage.

Animals↗

PubMed2002

Oligonucleotide microarray data mining: search for age-dependent gene expression.

Information on gene expression in colon tumors versus normal human colon was recently generated by an oligonucleotide microarray study. We used the associated database to search for genes that display age-dependent variations in expression. Statistically significant evidence was obtained that such genes are present in both the tumor and normal tissue databases. Besides the analysis of all genes included in the database, three subsets of genes were analyzed separately: genes controlled by p53, and genes coding for ribosomal proteins and for nuclear-encoded mitochondrial proteins. Among the genes controlled by p53 some show an age-dependent change in expression in tumor tissues, in the sense compatible with an activation of p53 at higher age. A decreased expression of some ribosomal genes at advanced age was detected both in tumor and normal tissues. No significant age-dependent expression could be detected for genes encoding mitochondrial proteins.

Adult↗

PubMed2002

An approach to increased polyplex gene delivery by peptides selected from a phage display library.

Phage display libraries were screened for peptides to be incorporated in nonviral gene delivery vehicles. Cells in culture were incubated with heptamer random peptide libraries displayed on M13 bacteriophages in three to five copies per phage. Surface-adherent phages were removed or inactivated and the cells were fractionated in a nuclear pellet and supernatant. Bacteriophages from each of the two fractions were amplified and reincubated with the cells. Three successive rounds of selection were performed. Eighteen sequenced clones revealed 14 different sequences. Two sequences were homologous to segments of the HIV gp120 protein. For three sequences, the corresponding synthetic peptides were generated and attached via avidin-biotin to polylysine-condensed plasmid DNA containing a reporter gene. The addition of the peptides led to 8-14 times increase in the expression of the reporter.

Amino Acid Sequence↗

PubMed2002

Regulated proteolysis of Xom mediates dorsoventral pattern formation during early Xenopus development.

To identify a regulatory role for proteolysis during early Xenopus development, we developed a biochemical screen for proteins that are degraded in an embryonic stage-specific manner. We found that Xom, a homeobox transcriptional repressor of dorsal-specific genes, was degraded precipitously during early gastrulation. Xom degradation is regulated by phosphorylation at a GSK3-like consensus site and is most likely mediated by the SCF-beta-TRCP complex. Expression of nondegradable Xom represses transcription of dorsal genes much more effectively than wild-type Xom and results in a more strongly ventralized phenotype. We propose that regulated Xom proteolysis plays an essential role in the establishment of the dorsoventral axis, by converting a gradient in BMP abundance into a sharp dorsoventral pattern.

Animals↗