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Effect of Cyclopamine on Xenopus laevis embryos

Anthony Sigismondo and Didier Alcarez, Franklin & Marshall College


Cyclopamine and jervine, teratogens derived from the skunk cabbage Veratrum californicum, are known to induce holoprosencephaly in chick embryos when introduced prior to gastrulation. Holoprosencephaly, a condition characterized by the reduction or apparent absence of left-right separation in certain tissues of the embryo, can be produced by a deficiency in the Sonic hedgehog signaling system. This disorder, also called cyclopia, results in offspring which are severely malformed and unable to survive due to serious brain defects.

Research performed by Michael K. Cooper and his associates showed that the presence of cyclopamine affects the signaling pathway of SHH in the early chick embryo. They claimed that cyclopamine acts as a class 2 transport inhibitor, a group of molecules which inhibit cholesterol esterification. These inhibitors seem to act by reducing the flow of cholesterol and its sterol precursors from the plasma membrane to the endoplasmic reticulum.

We planed on performing a study parallel to that performed by Cooper, only using Xenopus in place of chick embryos. Had we obtained similar results, then Xenopus and chick embryos may share common cues for signaling important information during development. This would illustrate that lower and higher vertebrates share common genetic programming.

By studying the growth of developing Xenopus embryos in cyclopamine solutions of varying molarity, obvious morphological mutations can demonstrate similarities between lower and higher vertebrates. If mutations are not found in the developing embryos, then SHH is yet another molecule whose function has changed throughout the course of evolution.

©Cebra-Thomas, 2000

Last Modified: 12 May 2000

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