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Biomedical subjects

R A Holmgren

Publications and source records attributed to R A Holmgren.

2 recordsLinked to original sources

Developmental potential.

In summary (and probably to no one's genuine surprise), it seems clear that some of the key themes in the mechanisms employed during development reiterate themselves throughout the animal kingdom. Yet, as our understanding becomes more refined, new and beguiling observations point to unique aspects of each developmental program. The concentration and absolute position of a variety of positional signaling molecules is likely to be very important in determinative events (establishment of the anteroposterior positioning in a field as in retinal development, establishment or enactment of a hox code, and selector gene regulation through gradients in Drosophila). Appropriate signalling responses are virtually certain to depend critically on the appropriate expression of each component of cellular signal transduction pathways (initiated by the activation of cell-surface receptor protein kinases to finally eliciting gene expression changes through the differential activity of specific transcription factors). The important biochemical details of transcription factor activation of specific respondent genes may be either simpler (as indicated from the murine/Drosophila domain swap experiments) or more complicated (from the responses of mim-1 to cellular versus viral myb proteins) than we had heretofore anticipated.

Animals

Cloning and characterization of the segment polarity gene cubitus interruptus Dominant of Drosophila.

The segment polarity mutation, cubitus interruptus Dominant (ciD), of Drosophila melanogaster causes defects in the posterior half of every embryonic segment. We cloned sequences from the ciD region on the proximal fourth chromosome by "tagging" the gene with the transposable element P. Genetic and molecular evidence indicates that the P-element insertions, which all occurred within the same restriction fragment, are in 5'-regulatory regions of the ciD gene within 3 kb of the first exon of its transcript. The putative ciD transcript was identified on the basis of its absence in homozygous ciD embryos. Its spatial pattern of expression during development is unusual in that, unlike most other segmentation genes, it exhibits uniform expression throughout cellular blastoderm and gastrulation and does not resolve into a periodic pattern until the end of the fast phase of germ-band elongation when it is present in 15 broad segmentally repeating stripes along the anterior-posterior axis of the embryo. Registration of the ciD stripes of expression relative to the stripes of other segment polarity genes shows that ciD is expressed in the anterior three-quarters of every segment. This registration does not correlate with the pattern defects observed in ciD mutants. Sequence analysis indicates that the protein encoded by the ciD transcript contains a domain of five tandem amino acid repeats that have sequence similarity to the zinc-finger repeats of the Xenopus transcription factor TFIIIA and that share the highest degree of identity with the human zinc-finger protein GLI, which has been found to be amplified in several human glioblastomas.

Amino Acid Sequence