Abstract of Thesis
University of California at Berkeley
August 2006
Notch signaling and segmentation in Parhyale hawaiensis

Segmented body plans occur in chordates, annelids, and arthropods, but whether the
process of segmentation arose once in a common ancestor or convergently is hotly debated.
To begin to settle this dispute, one must determine whether the same gene pathways are
utilized during segmentation among different phyla and within the same phylum.
Segmentation along the main body axis in arthropods has been characterized most
thoroughly in the fruitfly, Drosophila melanogaster, a long-germ insect that generates
segments simultaneously in a syncytial blastoderm by means of a hierarchical cascade of
genes. Most other arthropods sequentially specify their segments in a cellular environment
from an elongating posterior domain, in a manner at least superficially similar to that seen
during vertebrate somitogenesis. Vertebrates such as mice, frogs, and fish utilize the Notch
cell-signaling pathway to regulate the spatial and temporal periodicity with which segments
are generated during somitogenesis. In contrast, Drosophila does not require Notch during
segmentation along the main body axis, although Notch is required for segmentation and
growth control of the legs.

Despite differences in embryonic modes, short- and intermediate-germ insects, chelicerates,
and myriapods utilize portions of the Drosophila gene cascade to regulate segmentation, but
because most arthropod embryos have cellularized prior to deployment of these conserved
segmentation genes, there must be some means of communicating between cells in order
to establish and coordinate gene expression. Recently, segmentally iterated expression
patterns of an ortholog of Notch and several key components of the Notch signaling
pathway were described in the wandering spider, Cupiennius salei. Perturbation of the
pathway via RNAi-mediated depletion of the key components indicates a significant role
for Notch signaling during spider segmentation. In addition, an ortholog of Delta was
found to be segmentally expressed in a myriapod, Lithobius forficatus (Kadner and
Stollewerk, 2004).

To determine if Notch involvement during arthropod segmentation is confined to the
chelicerates and myriapods, believed to have branched basally from insects and crustaceans,
or if it is more widespread, I have cloned orthologs of Notch-pathway and downstream
target genes from the amphipod crustacean, Parhyale hawaiensis, and examined their
expression patterns. PhNotch expression is upregulated in a broad domain at the posterior
end of the germband, and PhDelta is expressed dynamically in the ectoderm at the
posterior of the Parhyale extending germband. I have also used the !-secretase inhibitor,
DAPT, to inhibit Notch signaling in Parhyale, resulting in segmentation defects not only
along the main body axis, but also in the antennae and abdominal appendages.
Additionally, expression of Phhes-1, an ortholog of the Drosophila hairy/enhancer of split family of transcription factors, is down-regulated following Notch inhibition with DAPT.
The expression patterns in Parhyale, coupled with the segmentation defects resulting from
Notch inhibition in Parhyale, suggest that Notch signaling may be used to coordinate the
expression of downstream segmentation genes in a wide array of arthropods.

Full Thesis

Selected Publications and Presentations:

O’Day K (2008) Lei Wang: Expanding the language of life. J Exp Med. 205: 2950-2951.

O’Day K (2008) Andrea Cooper: Using pathogens to probe the immune response. J Exp Med 205: 2690–2691.

O’Day K (2008) Gut reaction: Pyrosequencing provides the poop on distal gut bacteria. PLoS Biol 6: e295.

O’Day KE (2008) Researchers explore backback connection to back pain. BioMechanics 15(9): 39–45.

O’Day KE (2008) An enzymatic palimpsest. PLoS Biol 6: e217.

O’Day KE (2008) Shedding light on animal cryptochromes. PLoS Biol 6: e168.

O’Day KE (2008) Athletes get their game back after lumbar spine surgery. BioMechanics 15(5): 37–42.

O’Day KE (2008) Conspicuous chameleons. PLoS Biol 6: e21.

O’Day KE (2007) Secretory protein mRNA finds another way out. PLoS Biol 5: e330. doi:10.1371/journal.pbio.0050330

O’Day KE (2007) Omnidirectional electric fish. PLoS Biol 5: e314. doi:10.1371/journal.pbio.0050314

O’Day K (2007) Completing the Candida loop. PLoS Biol 5: e270. doi:10.1371/journal.pbio.0050270


Education:

Ph.D. Genetics and Development
UC Berkeley Department of Molecular & Cell Biology
Nipam H. Patel, advisor
9/2000-6/2006

B.A. Biochemistry and Molecular Biology
Mills College
Lisa Urry, advisor

B.A. Literature
New School for Social Research
MIA, advisor