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- W2591528048 abstract "ETV6/TEL1 (hereinafter referred to as TEL1) is an ets family transcription factor that is frequently involved in chromosomal translocations associated with leukaemia, including t(12:21) which generates the TEL-AML1 fusion gene, the most common genetic abnormality in childhood cancer. The role of TEL1 in normal haemopoiesis has been extensively studied in the mouse where knock-out studies have indicated that TEL1 is not required for development of primitive (ie yolk sac-derived) haemopoiesis. TEL1-knockout mice die at day E10.5 due to a defect in angiogenesis precluding direct analysis of the definitive (ie intraembryonically-derived) haematopoietic system. Analysis of chimaeric mice generated using TEL1−/− ES cells suggest that TEL1 is not required for generation of the definitive haemopoietic system during ontogeny but is required for HSC survival perinatally at bone marrow stages. Conditional knockout studies have subsequently identified a role for TEL1 in the survival of adult bone marrow-derived HSC. We now report the analysis of TEL1 function in amphibian ( Xenopus ) embryos where haemopoietic development can be studied even in embryos with defective angiogenesis. We characterised the TEL1 expression pattern and knocked down its function using antisense morpholino oligonucleotide injection. Consistent with the mouse knockout, specification of the primitive haemopoietic system was unaffected, however a defect in maturation of primitive erythroid cells, not previously reported in the mouse, was also apparent. We next analysed the development of the definitive haemopoietic system, thought to arise as clusters of HSCs in the floor of the dorsal aorta. But, no clusters of HSCs were found. Formation of the dorsal aorta however, proceeded normally, indicating that TEL1 controls the decision between the arterial and HSC programmes. Given, the critical role for TEL1 in the development of HSC indicated by these studies, a temporal analysis of emergence of intraembryonic HSC in TEL-deficient mice may be warranted." @default.
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- W2591528048 date "2005-11-16" @default.
- W2591528048 modified "2023-09-29" @default.
- W2591528048 title "ETV6/TEL1 Is Required for HSC Emergence during Embryonic Development." @default.
- W2591528048 doi "https://doi.org/10.1182/blood.v106.11.3607.3607" @default.
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