Fig. 5

Loss of Six3b/Six7 Is Epistatic to Loss of Spaw Function, and a Model for Six3 Function in Regulation of Diencephalic Nodal Activity (A) Control, uninjected embryo. (B) six3b^vu87/+ or six3b^vu87/vu87 injected with Spaw-MO1 (Long et al., 2003) (MO^spaw). lft1 expression is abolished in the diencephalon (arrowhead) and very strongly reduced in the posterior notochord (arrow). (C) six3b/six7-deficient embryo. (D) six3b/six7-deficient embryo injected with Spaw-MO1. Excessive, bilateral diencephalic lft1 expression is not abolished, but lft1 posterior notochord expression is strongly reduced. (E) In clutches comprising approximately 1:1 ratio of six3b^vu87/+ and six3b^vu87/vu87 embryos, inhibiting Spaw function abolishes lft1 diencephalic expression in 99% of embryos, inhibiting Six7 function causes bilateral lft1 expression in more than 40% of embryos (all six3b^vu87/vu87), and inhibiting both Spaw and Six7 results in restoring lft1 expression in 24% of embryos (all six3b^vu87/vu87). (F) A model of Six3 function and interaction with Nodal signaling during the establishment of early brain asymmetry. Six3 activity in the anterior neuroectoderm (light blue) and early Nodal signaling, presumably from the axial mesoderm (red), induce by early segmentation repressor/s of Nodal expression (X, dark blue) in the prospective dorsal diencephalon. Later, diencephalic left-sided expression of Nodal is achieved by ipsilateral Spaw, repressing X and activating Nodal. This results in correct epithalamic asymmetries (left-sided parapineal; higher lov levels [gray] in left habenular nucleus). P, pineal; pp, parapineal; lhn, left habenular nucleus; rhn, right habenular nucleus.