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6?and?Fig. 7, Supplemental Fig. 4). One possibility is that the left isomerized phenotype is dependent upon the distance between the divided pineal anlage. To test this hypothesis, we grouped the embryos based on parapineal YES1 phenotypes and measured the distance between the two most lateral points of the pineal ( Fig. 11). Pineal anlage were characterized as oval if their width was in the range of WT pineals, as elongated if there was a single domain that was wider than a normal pineal, and as divided if there was more than one domain. We find that the left isomerized phenotype is correlated to the severity of the open neural tube. When comparing embryos with open neural tubes, the pineal width of embryos with two bilateral parapineals is significantly greater than www.selleckchem.com/products/icotinib.html the pineal width in embryos with one parapineal (pThiazovivin clinical trial and one side of the brain develops as left and the other as right (Fig. 12). In contrast, in embryos with open neural tubes, this signal cannot function because the left and right sides are separated. Consequently, both sides develop gene expression patterns and morphology characteristic of the left side. This signal likely functions before formation of the parapineal organ, as midline defective mutants have switched from being left isomerized to having asymmetry by this stage of development (Fig. 12).