Figure 2.
Schematic representation of the stepwise development from mesodermal cells to HSPC/HSCs in the vertebrate embryo and the requirement of TGFβ signalling in these transitions based on current studies.
Decreasing BMP4 levels are needed from the mesodermal to a HE stage, and as a gradually decreasing gradient from the sub-aortic mesenchyme toward the ventral wall of the dorsal aorta. Within the ventral wall of the dorsal aorta, HE/HSPC/HSCs cells are activated by TGFβ1/3 and show presence of pSMAD2/3 and low pSMAD1/5/8. BMP4 is antagonised by BMPER, GREMLIN1a and NOGGIN. In our hypothesis, based on the published data, we postulate that SMAD2/3 is needed to open the chromatin for Runx1 to drive EHT, in a process similar to that seen in EndoMT. Please note that the scheme does not include other known regulators of Runx1 expression such as Notch or VegfA signalling.