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lab profile
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Gunter Wagner Yale University
300 Heffernan Dr., #B31
West Haven, CT 6516
USA
gunter.wagner@yale.edu
203-737-3091
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| PI: |
YES |
| Taxa Studied: |
Vertebrate Animals |
| Techniques Employed: |
Quantitative PCR (qPCR), Sanger Sequencing, Bioinformatics/Sequence Analysis, Antibody Staining, RNA interference(RNAi), Sectioning for Histology, Morpholinos, Mutagenesis |
| Research Description: |
We are interested in the genetic changes that underlie the evolution of cell types. Our model system is the decidual stromal cell type, which plays a key role in mediating the fetal-maternal interaction during pregnancy in mammalian species that exhibit invasive placentation. Physiologically, decidual stromal cells develop from endometrial stromal fibroblasts upon activation of several signaling pathways. Endometrial stromal fibroblasts are present in the uterus of both marsupials and eutherians, but the decidual stromal cell type is a eutherian-specific novelty. Currently we are investing what genetic changes were responsible for the evolution of the decidual stromal cell type in the stem eutherian lineage. We have identified two transcription factors, homeobox A11 (HoxA11) and CCAAT/enhancer-binding protein beta (C/EBPß), which have undergone trans-regulatory changes, or protein-coding sequence changes, in the stem-eutherian lineage. As a result, these proteins cooperatively interact with another transcription factor, forkhead box O1 (FoxO1), to regulate the expression of a large set of downstream genes that are markers of the decidual stromal cell type. The evolutionary consequence of these novel protein-protein interactions was amplified by the concurrent changes in the distribution of the eutherian-specific transposable element MER20, which contains the combined binding sites for these transcription factors. Importantly, FoxO1 is not expressed in the endometrial stromal fibroblasts of Monodelphis domestica, a marsupial species, which raises the possibility that the cis-regulatory recruitment of FoxO1 occurred concurrently with the trans-regulatory evolution of HoxA11 and C/EBPß to form the gene regulatory network responsible for the decidual stromal cell type identity. The case of decidual stromal cell type shows that the emergence of a cell type is preceded by the evolution of a network of various types of genetic changes. |
| Lab Web Page: |
http://www.yale.edu/gpwagner/ |
| Willing to Host Undergraduates: |
NO |
| Actively Seeking Undergraduates: |
NO |
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