Suppression of tadpole limbs: a model for organ size regulation

Duquesne University, Pittsburgh PA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Body size can be altered by pituitary growth hormone, with the largest and smallest nonobese humans varying by about 10-fold in body mass. Organ sizes generally vary with body size, although there are indicators of local organ size regulation as well. A well-known case of organ suppression, namely limbs in the frog's tadpole, will be used to identify potential regulators of organ size. Tadpole limbs arise late and develop slowly. Conversely, there are frog species, known as direct developers, in which there are no tadpoles and in which limbs develop early and rapidly as in mammals. These different paths provide opportunities for comparison to identify molecular and cellular steps involved in limb suppression in tadpoles. First, expression of genes, known to be involved in limb development, will be examined in tadpoles to see when and where delays occur. One focus will be on cells destined to form muscle, which migrate into the limb bud. This survey of gene expression will pinpoint steps to investigate in detail. Second, the tissue responsible for the limb suppression in tadpoles will be identified by tissue transplantation between embryos of the tadpole species and the direct developing species. Third, three potential regulators of organ size will be examined for a role in tadpole limb suppression, initially by determining whether their genes are expressed in limb buds. The potential regulators are the Hippo signaling pathway, Hairy genes, and microRNAs. Genes of the Hippo signaling pathway are implicated not only in organ size regulation in fruit flies, but also in human cancers. Hairy genes code for repressors of genes, and they can reduce wing development in chick embryos. MicroRNAs inhibit protein production and are involved in development, normal cellular activities, and cancers. Suppression of tadpole limb development provides a novel system for testing further regulatory activities of these molecules, already implicated in human diseases. PUBLIC HEALTH RELEVANCE: Legs of tadpoles develop late and grow slowly compared to legs of other embryos, including humans. This suppression of tadpole limbs provides a novel context to investigate mechanisms that control size of organs. In addition, several of the candidates for size control are implicated in human cancers. [unreadable] [unreadable] [unreadable]