Figure 4. FGF signaling controls brain asymmetry through regulation of six3 transcription factor expression.

(A, B) Dorsal view of a 12–14 somite embryo with head dissected away from yolk, showing expression of six3b. six3b is expressed broadly in the eye fields and brain, including the dorsal diencephalon (black arrow) of the developing embryo in DMSO control (A; n=75), but is diminished in SU5402 embryos (B; WT=81), including in the diencephalon (red arrow). (C, D) Dorsal view of a 12–14 somite embryo with head dissected away from yolk, showing expression of six7. six7 is expressed broadly in the eye fields and brain, including the dorsal diencephalon (black arrow), of the developing embryo in DMSO control (C; n=48), but is diminished in SU5402 embryos (D; n=51), including in the diencephalon (red arrow). (E) Histogram quantifying the % of embryos expressing WT levels of both six3b and six7 in DMSO Control and SU5402 treated embryos. (F–I) Dorsal view of a 12–14 somite control or caFGFR transgenic embryos, with head dissected away from yolk, showing expression of six3b Embryos were HS activated at 4–6 somites to have maximal activation of FGF signaling at 8 SS to parallel the SU5402 studies. Six3b expression is upregulated in caFGFR transgenic HS’d embryos (I) compared to non-transgenic non HS’d (F; white bracket showing dorsal diencephalon staining), caFGFR transgenic HS’d (G), and non-transgenic HS’d embryos (H). (J–M) Dorsal view of a 12–14 somite control or caFGFR transgenic embryos, with head dissected away from yolk, showing expression of six7. (M) Six7 expression is absent in the dorsal diencephalon of caFGFR transgenic HS’d embryos compared with non-transgenic non HS’d (J; white bracket showing dorsal diencephalon staining), caFGFR transgenic non HS’d (K), and non-transgenic HS’d embryos (L). (O) Histogram quantifying six3b expression in caFGFR genotyped embryos. (P) Histogram quantifying six7 expression in caFGFR genotyped embryos.