Abstracts - Society for Developmental Biology

108
hyperplastic lesions lose stratification of the luminal and basal layers and increase in CK5+/CK8+/CK18+ cell population.
Interestingly, the lack of stratification is coupled with a loss of apical-basolateral polarity, which leads to formation of
ectopic microlumens. Together, these results demonstrate that Gata3 controls a transcriptional program in the prostate buds
important for lineage specification and stratification of the prostate epithelium.
Program/Abstract # 327
Investigating the role of the transcription factor Gata3 during post-natal prostate development
Shafer, Maxwell, McGill University, Montreal, Canada; Nguyen, Alana; Bouchard, Maxime (McGill University,
Montreal, PQ, Canada)
The prostate develops at the base of the bladder in the mass of tissue known as the urogenital sinus (UGS). Epithelial cells
branch from the UGS and form morphologically distinct ducts composed of differentiated basal, luminal and
neuroendocrine cell types. This process, and the concomitant differentiation of the luminal and basal cells of the prostate,
may be mediated by controlled cell division and differentiation during both organogenesis and the development of prostate
cancer. The aim of this project is to investigate the role and targets of Gata3 during prostate development, and in
particular, its function in prostate stem cell homeostasis and cellular differentiation. Preliminary and current results
obtained in the laboratory have established that the loss of Gata3 in early prostate development leads to prostate dysplasia,
cellular hyperplasia of the basal and luminal compartments, and defects in cell lineage specification. On the basis of these
results, we hypothesize that Gata3 regulates key effectors of stem/progenitor cell homeostasis, division and differentiation.
Standard molecular and biochemical techniques such as immunocytochemistry, in situ hybridization and confocal
microscopy will be used to investigate the expression and function of Gata3 and its downstream target genes in the first
two weeks of post-natal prostate development in the mouse. We will take advantage of the Cre-lox technology, which
allows prostate specific gene knockouts, to modify the expression of Gata3 and its target genes during development in
prostate tissue. Tissue transplantation will be used to introduce genetically modified prostate stem cells (gene knock outs)
into wildtype mice to investigate the function of Gata3 and its targets in the development of prostate tissue. This research
may lead to the discovery of therapeutic targets for the treatment and/or prevention of prostate cancer and contribute to our
understanding of the embryonic development of an important regulatory organ.
Program/Abstract # 328
Novel shadow enhancers regulate HoxB gene expression during heart and gut development
Nolte, Christof D.; Krumlauf, Robb, Stowers Institute for Medical Research, Kansas City, United States
During vertebrate development, the heart is one of the first functioning organs to form. In bird and mammal embryos it
develops from two distinct mesodermal populations defined as the first and second heart field (FHF and SHF,
respectively). The left ventricle is derived from the FHF while the right ventricle and outflow tract are derived from the
SHF. Work in both invertebrates and vertebrates has defined many of the essential regulators for cardiac specification and
differentiation, however the genes and the coordination of the signaling pathways that orchestrate the patterning within
these fields are poorly understood. Recently, members of the HoxA and HoxB clusters have been shown to be
differentially expressed and important in patterning the murine heart. However the mechanisms that regulate these Hox
activities are unknown. In regulatory analyses of the HoxB cluster we have identified an enhancer region that directs
dynamic expression in the SHF in addition to expression throughout the adjacent endoderm. In light of the key role of
retinoic acid (RA) in heart development, we explored links between this region and retinoid signaling. The enhancer
displays a robust response to exogenous RA and we identified a retinoic acid response element (RARE) in the region.
Deletion analysis of the enhancer suggests that it integrates multifactorial inputs that may involve members of the GATA
transcription family in addition to the retinoid receptors. In a BAC transgenic assay, the region appears to function as a
shadow enhancer to control elements present near the Hoxb1 gene to ensure correct expression of HoxB genes during
cardiac development.
Program/Abstract # 329
The role of Hoxa3 in the developing 3rd pharyngeal pouch endoderm and its derivatives, early and late
Chojnowski, Jena L.;Masuda, Kyoko; Trau, Heidi; Manley, Nancy, University of Georgia, Athens, United States
Homeobox (Hox) genes encode an evolutionarily conserved family of transcription factors involved in numerous
developmental pathways. Mouse Hoxa3 is expressed in the pharyngeal region, including the endoderm and the neural crest
derived mesenchymal cells (NCCs). It is required for the development of the third and fourth pharyngeal pouch-derived
organs, including the thymus and the parathyroids. Global deletion of Hoxa3 early in development, before pharyngeal
pouch development, prevents both thymus and parathyroid initial organogenesis. The loss of Hoxa3 in the NCCs prevents
proper migration of the thymus and parathyroid by blocking their separation from the pharynx and each other but it has no