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Updated: Aug 14, 2026
Derivation of Mouse Trophoblast Stem Cells from Blastocysts
Published on: June 8, 2010
Defective trophoblast function in mice with a targeted mutation of Ets2
H Yamamoto1, M L Flannery, S Kupriyanov
1The Burnham Institute, La Jolla, California 92037, USA. rgoshima@ljcrf.edu
Abstract:
Members of the Ets family of transcription factors mediate transcriptional responses of multiple signaling pathways in diverse cell types and organisms. Targeted deletion of the conserved DNA binding domain of the Ets2 transcription factor results in the retardation and death of homozygous mouse embryos before 8.5 days of embryonic development. Defects in extraembryonic tissue gene expression and function include deficient expression of matrix metalloproteinase-9 (MMP-9, gelatinase B), persistent extracellular matrix, and failure of ectoplacental cone proliferation. Mutant embryos were rescued by aggregation with tetraploid mouse embryos, which complement the developmental defects by providing functional extraembryonic tissues. Rescued Ets2-deficient mice are viable and fertile but have wavy hair, curly whiskers, and abnormal hair follicle shape and arrangement, resembling mice with mutations of the EGF receptor or its ligands. However, these mice are not deficient in the production of TGFalpha or the EGF receptor. Homozygous mutant cell lines respond mitogenically to TGFalpha, EGF, FGF1, and FGF2. However, FGF fails to induce MMP-13 (collagenase-3) and MMP-3 (stromelysin-1) in the Ets2-deficient fibroblasts. Ectopic expression of Ets2 in the deficient fibroblasts restores expression of both matrix metalloproteinases. Therefore, Ets2 is essential for placental function, mediating growth factor signaling to key target genes including MMP-3, MMP-9, and MMP-13 in different cell types, and for regulating hair development.
Insights
The Ets2 transcription factor is crucial for embryonic development, placental function, and hair formation. Its absence causes embryonic lethality and defects in matrix metalloproteinase gene expression.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Ets transcription factors regulate gene expression in response to signaling pathways.
- Ets2 plays a role in various cellular processes and organismal development.
Purpose of the Study:
- To investigate the essential role of the Ets2 transcription factor in mouse embryonic development and extraembryonic tissue function.
- To determine the downstream targets and signaling pathways regulated by Ets2.
Main Methods:
- Targeted deletion of the Ets2 DNA binding domain in mice.
- Tetraploid embryo complementation assay for rescuing developmental defects.
- Analysis of gene expression, including matrix metalloproteinases (MMPs), in Ets2-deficient cells and embryos.
- Mitogenic response assays to growth factors (TGFα, EGF, FGF).
Main Results:
- Homozygous Ets2-deficient embryos exhibit developmental retardation and lethality before 8.5 days, with defects in extraembryonic tissues.
- Ets2 deficiency leads to reduced expression of MMP-9, persistent extracellular matrix, and impaired ectoplacental cone proliferation.
- Rescued Ets2-deficient mice show abnormalities in hair development, including wavy hair and abnormal follicle morphology.
- Ets2 is essential for FGF-induced expression of MMP-13 and MMP-3 in fibroblasts, which is restored upon Ets2 re-expression.
Conclusions:
- Ets2 is indispensable for proper placental function and embryonic survival.
- Ets2 mediates growth factor signaling to regulate key target genes, including MMP-3, MMP-9, and MMP-13.
- Ets2 plays a critical role in the development and regulation of hair follicles.
