Research in Bea Holton's lab
Dr. Beatrice Holton studies the modulation of tension across tissues
by examining the formation of the chick chorioamniotic membrane (ChorAm).
The ChorAm begins formation as a fold of tissue at the anterior end
of the embryo. This fold rises above the head, collapses over the head
and then is drawn down the body of the embryo until it finally envelopes
the entire embryo. By several means, it has been possible to show that
tension exists in the leading edge and along the midline of the ChorAm
and that this tension is important to the alignment of the embryo. Furthermore,
preliminary results from Holtons laboratory indicate that programmed
cell death (that occurs at the leading edge) and amount of tension are
interrelated. When tension is increased across the membrane, cell death
decreases and when tension is relaxed cell death increases. Additional
preliminary results show that beta-catenin, a transcription factor that
also complexes with points of cell/cell adhesion and microfilaments
localizes to cells that are in or near the leading edge. Perhaps this
protein and its downstream targets sense degree of tension. Thus, Holton
would like to begin investigating signal transduction proteins that
are likely to be involved in sensing tension and in relaying the signal
so that programmed cell death is stimulated or inhibited. Holton assumes
that this process would involve changes in gene expression. Studies
such as these are important because multiple developmental processes
involve or may involve tension sensing: body wall closure, wound sensing
and healing. The goal of REU student projects would be to identify differences
in gene expression between cells under tension (along the leading edge
of the ChorAm) and cells lacking tension (cells back from the leading
edge). The student(s) would do this by isolating RNA from the two populations
of cells then by using microarrays and/or differential display analysis
to look for differences in gene expression. Student(s) would investigate
both approaches to determine which had the most potential. Microarray
analysis would be ideal for this type of study; however, chicken microarrays
do not yet exist, so the student would use mouse arrays and depend on
gene homology for interpretable results.



