Fig. 6.

The regulatory state and VEGF downstream GRN in the skeletogenic cell clusters during the initiation of spiculogenesis. (A–F) Spatial expression and response to VEGFR inhibition at the initiation of spiculogenesis (23–25 hpf) of the genes encoding the transcription factors, Ets1/2 (A), Erg (B), Hex (C), Tel (D), FoxO (E), and Alx1 (F), n ≥ 3. VV, vegetal views in control embryos. (Magnification, 200×.) (G) Model of the regulatory network at the skeletogenic clusters at the time of spiculogenesis (24 hpf). The regulatory interactions between the upstream transcription factors were studied only at earlier stages (6) and are therefore indicated by dashed lines. TF refers to the transcription factor that mediates VEGFR signaling. Blue gene names indicate skeletogenic specific genes and black names indicate genes common to both spiculogenesis and vascularization (56–60, 88–90). Arrows indicate activation and bars represent repression. Thick links indicate regulatory interactions observed in vertebrates’ hemangioblast differentiation (90) or in human endothelial cells (88, 89) (Dataset S4).