Patricia A. Labosky, PhD

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				Patricia A. Labosky, Ph.D. Asst. Prof., Cell and Developmental Biology 1109 Biomedical Research Building II/III 215-573-7547 FAX: 215-898-9871 email: plabosky@mail.med.upenn.edu http://www.med.upenn.edu/cellbio/faculty/labosky/index.html Click here for selected publications since Dr. Labosky's arrival at Penn RESEARCH INTERESTS development of the mammalian embryo, genes that control neuronal patterning, gastrulation, neural crest specification and multipotency of stem cells. RESEARCH TECHNIQUES Transgenic mice, gene targeting (knock-outs and knock-ins), culturing of embryonic stem cells (ES cells) and trophoblast stem cells (TS cells), dissection of mouse embryos from all stages, histological techniques such as immunohistochemistry and in situ hybridizations. Standard molecular biology techniques including recombinant DNA PCR, Southern and northern blot hybridizations. We are also using lacZ and Green Fluorescent Protein (GFP) as lineage markers for both Foxb1 and Foxd3 expressing cells. RESEARCH SUMMARY My lab is interested in studying the genes that control normal development of the mammalian embryo. We have focused this work on a group of transcription factors from the "winged helix" or "forkhead" family. Many of these genes are expressed in restricted patterns in the central nervous system and body axis of the developing mouse embryo and have been shown to play a role in the regulation of cell proliferation. Several members of the family also play roles in the progression of cancerous tumors and disease. The WH gene Foxd3 (previous Hfh2 or Genesis) is expressed in the early preimplantation embryo, in ES cells and then later in the neural crest. The neural crest is a multipotent lineage that gives rise to neurons, glia, smooth muscle, cartilage and other tissues. Our previous work established Foxd3 as a gene crucial for stem cell fate in the early mouse embryo. Without the function of this gene the embryos die around implantation and ES cells cannot be established. This makes Foxd3 one of only a handful of genes identified as required for these events. Ongoing experiments will test the effects of increasing and reducing the levels of Foxd3 by overexpression and siRNA in ES cells. Foxd3 is also expressed later in the embryo in neural crest cells. This later expression pattern is particularly enticing as it makes Foxd3 one of the earliest markers of neural crest in the mouse. Overexpression of Foxd3 in chick embryos (in collaboration with Dr. Martyn Goulding at the Salk Institute) has shown that Foxd3 is sufficient to specify the neural crest cell lineage. Several other mis-expression experiments are underway to determine whether Foxd3 also has the ability to induce neural crest cell fate in the mouse and/or confer stem cell fate in different niches. We are currently generating a tissue specific deletion of Foxd3 using the Cre-LoxP system to selectively mutate the gene in only the neural crest cells.