Notch Regulation of Hematopoiesis, Endothelial Precursor Cells, and Blood Vessel Formation: Orchestrating the Vasculature

Figure 2

Scheme showing the essential functions of Notch in blood and vascular cell types (a) Osteocyte Dll/Jag-induced Notch signaling in hematopoietic stem cells (HSCs) is involved in their generation and self-renewal in the adult. (b) Notch signaling pathway is required for endothelial progenitor cells (EPCs) development and function. EPCs from bone marrow niches will, in response to Notch, differentiate in endothelial cells (ECs) and populate sites of ischemia participating in vascularization. (c) Schematic representation of a growing blood vessel. In angiogenesis, Notch ligand DLL4 is upregulated in response to VEGF/VEGFR2 signaling in tip cells, that are specified ECs (dark yellow) capable of sprouting by extending filopodia. Upregulated DLL4 in tip cells activates Notch in the neighbor stalk ECs (light yellow) inhibiting their sprouting capacity. Notch activation in stalk cells will result in further DLL4 upregulation, which eventually will activate Notch in adjacent cells. SMCs, covering the endothelium are represented in green. (d) Notch induces arterial specification of ECs by upregulating the expression of arterial markers, such as EphrinB2. The lack of Notch in venous endothelial cells allows the expression of venous markers, such as COUP-TFII. Notch regulates also smooth muscle cell (SMC) differentiation by inducing the expression of SMC-specific markers (e.g., αSMA, SM-MHC, SMα22, and SM calponin).