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Figure 3. Tadpole craniofacial anomalies caused by injection of mRNA for KCNJ2 variants. Anterior is up in all panels; view is dorsal except in D–F, J, M, Q and U. All scale bars = 0.5 mm. A-F, normal wildtype head of the stage 46 tadpole. A and D, darkfield; B and E, Alcian blue staining; C and F, after Reisoli et al. (2010). G–U, both the range of phenotypes seen and the commonality of the phenotypes resulting from all the variants tested. G–K, heads of tadpoles that were injected with the dominant negative Kcnj2 variant D71V. Illustrated are typical anomalies: G, small eye; H, fusion of the two olfactory bulbs; I, pigmented optic nerve and missing eye; J, anomalies restricted to one side include a small misshapen eye with misplaced lens, grossly undersized branchial arches and malformed Meckel's cartilage; K,fusion of the brain eye and olfactory bulb on the right side. L–P, heads of tadpoles injected with T192A. L, the leftmost arrow points to a malformed olfactory bulb, while the other two arrows point to the same anomalies seen in D71V-injected tadpoles J and K, namely malformed Meckel's cartilage and fusion of the brain with the eye. M, another commonly seen malformation is the narrowing of the anterior most end with malformed or absent infraostral [sic infrarostral] and Meckel's cartilages. N, an example of a more subtle phenotype of differences in size of Meckel's cartilages and the branchial arches. O, a commonly seen eye phenotype, shown in an tadpole with bilateral anomalies. In these tadpoles the optic nerve is both pigmented and thickened, looking like an extension of the eye. This embryo also has a malformed olfactory bud [sic bulb]. P, this embryo shows the same inequality of Meckel's cartilages seen in N, combined with gross malformations of both eyes. The otic capsule is also misshapen in this tadpole. Q and R, tadpoles expressing the Y242F variant. Q, the ceratohyals of this tadpole are badly distorted, while at least one of Meckel's cartilages is located in the wrong place. The right eye of this tadpole lacked a lens. R, a more subtle effect of Y242F showing distorted ethmoidal plate, a badly positioned eye, and, like the D71V tadpole in J, small branchial arches on one side. S, similar phenotypes are caused by injection of a different potassium channel, including abnormal narrowing anteriorly and concomitant loss of Meckel's cartilages and probably the infraostral cartilage [sic infrarostral), fusion of the olfactory bulb and eye, misshapen eye, and a misshapen otic capsule, like the T192A-injected tadpole in P, which lacks an otolith. T and U, tadpoles grown from R218W-injected embryos. T, this tadpole has distorted Meckel's cartilages and quadrate, malformed eyes, malformed ethmoidal plate, and small branchial arches on one side. U, deformed Meckel's and ceratohyal cartilages, one bad eye and small branchial arches, resulting from R218W injection as well as injection of the other variants.

Image published in: Adams DS et al. (2016)

Copyright © 2016. This image is reproduced with permission of the publisher and the copyright holder. This is an Open Access article distributed under the terms of the Creative Commons Attribution License.

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