Effect of lithium on fish development

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Discussion

These results demonstrate that lithium chloride treatment affected the anterior-posterior morphogenesis of Brachydanio rerio embryos such that higher concentrations of this substance lead to increasingly greater inhibition of anterior and posterior development. The 0.15 M LiCl-treated embryo were missing their anteriormost structures. The embryos treated with 0.30 M LiCl exhibited greater teratogenic effects on the development of anterior and posterior terminus structures. Higher concentrations of LiCl also led to more morphological defects in both the anterior and posterior terminal regions, further confirming the hypothesis that the concentrations of LiCl teratogen is directly related to the phenotypic effect on Zebrafish.

Lithium-induced teratogenesis has been shown to perturb the development of ventral structures in premidblastular Zebrafish, when the blastula is still forming morphogenetic gradients of proteins in the Wnt signaling pathway (such as b-catenin) and continuing to transcribe maternal mRNAs. In these early embryos, lithium teratogenesis leads to the expression of bustled and radialized phenotypes, which exhibit hyperdorsalization (Stachel et. al., 1993). In the sphere-stage embryos, morphogenetic gradients have already been established, so the effect of lithium in this case probably occurs downstream of these events.

Studies conducted by Stewart and Gerhart (1990) showed that lithium inhibits gastrulation movements in Xenopus, resulting in incomplete involution and thus incomplete induction of anterior structures (Stewart and Gerhart, 1990). This could possibly indicate that lithium teratogenesis perturbs development in later embryos by preventing gastrulation.However, the phenotype of lithium-treated Zebrafish embryos does not appear to be equivalent to that of Xenopus embryos. The most striking effect is on the normal formation of structures anterior to the eye. Stachel and coworkers (1993) have presented evidence of the normal development of central nervous system structures anterior to the presumptive eye region when lens and retina develop abnormally. This suggests that the incomplete gastrulation model of lithium teratogenesis in Xenopus does not fully explain the phenotypic effects of lithium in Brachydanio rerio embryos. This evidence also suggests that there may be differential signaling patterns involved in Xenopus as compared to Zebrafish eye formation.

Lithium dorsalizes sea urchin embryos by increasing the levels of b-catenin throughout the cytoplasm, which leads to the radialization of goosecoid expression and subsequent augmentation of organized mesoderm throughout the marginal zone and into the presumptive ventral regions of the embryo (Gilbert, 2003). The embryos in this experiment did not show a great degree of dorsalization, except possibly the 0.45 M LiCl embryo, but further tests would need to be conducted before determining whether or not lithium induces dorsal specification of tissues.

Fortunately, such studies have been conducted by Stachel and colleagues (1993). They used a fluorescent market gene intercalated in the genome adjacent to the goosecoid transcript, so that the marker appears in the wherever goosecoid protein is present. The results of their experiment on lithium induction in Zebrafish shows that the distribution of goosecoid transcripts increases substantially ten hours after development. During this period, rostral crescent swelling and medial strip patterns usually exhibiting goosecoid transcripts appear normal. However, the lateral wings, areas of goosecoid expression found in normal embryos, are missing, which suggests that late-lithium exposure either reduces transcription of goosecoid in the lateral wing region or prevents cell movements directing the anterolateral accumulation of goosecoid (Stachel et. al., 1993). This reduction in the expression of goosecoid in the anterolateral region suggests that lithium is partially responsible for the inhibition of normal anterior development.

J. N. White 5/13/04

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		Discussion These results demonstrate that lithium chloride treatment affected the anterior-posterior morphogenesis of Brachydanio rerio embryos such that higher concentrations of this substance lead to increasingly greater inhibition of anterior and posterior development. The 0.15 M LiCl-treated embryo were missing their anteriormost structures. The embryos treated with 0.30 M LiCl exhibited greater teratogenic effects on the development of anterior and posterior terminus structures. Higher concentrations of LiCl also led to more morphological defects in both the anterior and posterior terminal regions, further confirming the hypothesis that the concentrations of LiCl teratogen is directly related to the phenotypic effect on Zebrafish. Lithium-induced teratogenesis has been shown to perturb the development of ventral structures in premidblastular Zebrafish, when the blastula is still forming morphogenetic gradients of proteins in the Wnt signaling pathway (such as b-catenin) and continuing to transcribe maternal mRNAs. In these early embryos, lithium teratogenesis leads to the expression of bustled and radialized phenotypes, which exhibit hyperdorsalization (Stachel et. al., 1993). In the sphere-stage embryos, morphogenetic gradients have already been established, so the effect of lithium in this case probably occurs downstream of these events. Studies conducted by Stewart and Gerhart (1990) showed that lithium inhibits gastrulation movements in Xenopus, resulting in incomplete involution and thus incomplete induction of anterior structures (Stewart and Gerhart, 1990). This could possibly indicate that lithium teratogenesis perturbs development in later embryos by preventing gastrulation.However, the phenotype of lithium-treated Zebrafish embryos does not appear to be equivalent to that of Xenopus embryos. The most striking effect is on the normal formation of structures anterior to the eye. Stachel and coworkers (1993) have presented evidence of the normal development of central nervous system structures anterior to the presumptive eye region when lens and retina develop abnormally. This suggests that the incomplete gastrulation model of lithium teratogenesis in Xenopus does not fully explain the phenotypic effects of lithium in Brachydanio rerio embryos. This evidence also suggests that there may be differential signaling patterns involved in Xenopus as compared to Zebrafish eye formation. Lithium dorsalizes sea urchin embryos by increasing the levels of b-catenin throughout the cytoplasm, which leads to the radialization of goosecoid expression and subsequent augmentation of organized mesoderm throughout the marginal zone and into the presumptive ventral regions of the embryo (Gilbert, 2003). The embryos in this experiment did not show a great degree of dorsalization, except possibly the 0.45 M LiCl embryo, but further tests would need to be conducted before determining whether or not lithium induces dorsal specification of tissues. Fortunately, such studies have been conducted by Stachel and colleagues (1993). They used a fluorescent market gene intercalated in the genome adjacent to the goosecoid transcript, so that the marker appears in the wherever goosecoid protein is present. The results of their experiment on lithium induction in Zebrafish shows that the distribution of goosecoid transcripts increases substantially ten hours after development. During this period, rostral crescent swelling and medial strip patterns usually exhibiting goosecoid transcripts appear normal. However, the lateral wings, areas of goosecoid expression found in normal embryos, are missing, which suggests that late-lithium exposure either reduces transcription of goosecoid in the lateral wing region or prevents cell movements directing the anterolateral accumulation of goosecoid (Stachel et. al., 1993). This reduction in the expression of goosecoid in the anterolateral region suggests that lithium is partially responsible for the inhibition of normal anterior development.
		J. N. White 5/13/04