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Fig. 1. RUNX1 dosage in hematopoietic development. (A) Schematic representation of the two most abundant RUNX1 isoforms. Except for the most N-terminal sequence (RUNX1C N-terminal in green, RUNX1B N-terminal in red) the proteins are identical and they both contain the highly conserved Runt homology domain (RHD, blue) followed by a transactivation domain (TAD, orange) which is flanked by inhibitory regions. The C-terminal inhibitory region contains a highly conserved VWRPY motif (brown). (B) Immunofluorescence on the AGM of a E10.5 mouse embryo. The dorsal aortic endothelial cells are marked by the endothelial marker CD31 (yellow). The majority of the cells on the ventral side of the dorsal aorta (constituting both endothelial and rare HE cells) are positive for the RUNX1 protein (magenta). Scale bars = 20 μm. (C) Current model of RUNX1 dosage in hematopoietic development. Top: RUNX1 dosage requirement can be divided in three phases. Phase ①: early in differentiation RUNX1 is not required but its (low) dose influences the timing and dynamics of HE cells appearance. Phase ②: although RUNX1 levels are still low in HE cells, its presence is required for the initiation of the EHT. Phase ③: an increased dose of RUNX1 is required for the completion of EHT and the generation of the first mature hematopoietic cells. The whole differentiation process is predominantly controlled by the RUNX1b isoform. Bottom: schematic overview of the currently available phenotypic data on RUNX1 dosage during the establishment of the hematopoietic system in the embryo.
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