Figure 10. A model for parapineal organ and the habenulae defects in sox2 morphants.

(A) In control embryos, the Nodal signaling is activated on the left side of the diencephalon and leads to the upregulation of the bilaterally expressed fgf8a on the left side. The Nodal and fgf8a signals are important for the leftward migration of the parapineal organ, which specifically innervates the left habenula. As a result, the left habenula is larger than the right. (B) In a subset of sox2 morphants, Nodal signaling is bilaterally active leading to randomization of the parapineal laterality and consequently randomization of the habenular asymmetries. In addition, some sox2 morphants have bilateral parapineal organs, possibly due to abnormal cell-adhesion properties. yellow = diencephalon, blue = pineal gland, red = parapineal cells (dotted lines surrounding parapineal cells represent defective cell-adhesion), orange = habenulae and their projections, purple = interpeduncular nucleus; the main habenular target.