POWRE: Molecular Mechanisms of Thyroid Hormone Action on Stem Cells

9805900霍斯金斯在这项由POWRE奖资助的研究中，霍斯金斯博士将研究青蛙眼睛在变态过程中发生变化的分子基础。小蝌蚪的眼睛位于头部两侧，两只眼睛可以看到视觉世界中不重叠的区域。在变形过程中，头部改变形状，眼睛一起移动，结果是成年青蛙有双目视觉--视觉世界的一部分用两只眼睛看到，就像人类的情况一样。在由甲状腺激素引起的从蝌蚪到青蛙的转变过程中，眼睛内部以及眼睛和大脑之间的连接都会发生许多变化。霍斯金斯实验室之前的工作表明，甲状腺激素诱导了一种特定的新的视网膜生长模式，并在变形过程中产生了一组新的视神经轴突。这些新的研究将解决甲状腺激素如何触发视网膜生长的变化，以及在变形过程中形成的新轴突如何能够连接到它们合适的目标的问题，这与蝌蚪轴突建立的连接模式不同。甲状腺激素通过一种能够改变基因表达模式的受体起作用；因此，在视网膜中表达的激素诱导的基因似乎可能在视觉系统的变性转变中发挥作用。所有动物的神经系统，包括人类，都依赖于甲状腺激素才能正常发育。霍斯金斯博士的实验系统为研究甲状腺激素在发育过程中的作用机制提供了一个独特的可访问和可操作的模型，这些研究的结果有望与甲状腺激素在神经元发育中的一般作用相关。POWRE奖将允许一位具有重大教学职责的优秀研究人员开始一项研究项目，使用新的分子方法论来研究她长期感兴趣的系统和问题。

9805900 HOSKINS In the study funded by this POWRE award, Dr. Hoskins will examine the molecular basis of changes that occur in the frog eye during metamorphosis. The eyes of young tadpoles are situated on the sides of the head and the two eyes view non- overlapping regions of the visual world. During metamorphosis, the head changes shape, and the eyes move together, with the result that adult frogs have binocular vision -- parts of the visual world are seen with both eyes, as is the case in humans. During the transition from tadpole to frog, which is brought about by thyroid hormone, numerous changes occur both within the eye and in the connections between the eye and the brain. Previous work from the Hoskins laboratory showed that thyroid hormone induces a specific new pattern of retinal growth, and that a new set of optic nerve axons are produced during metamorphosis. These new studies will address the question of how thyroid hormone triggers changes in retinal growth, and how the new axons formed during metamorphosis are able to connect to their proper targets, which differs from the pattern of connections made by tadpole axons. Thyroid hormone acts through a receptor that is capable of changing the pattern of gene expression; it therefore seems likely that hormone-induced genes expressed in the retina will play a role in the metamorphic transformations in the visual system. The nervous systems of all animals, including humans, are dependent on thyroid hormone for proper development. Dr. Hoskins' experimental system offers a uniquely accessible and manipulable model for examining the mechanisms of thyroid hormone action during development, and the results of these studies are expected to be relevant to its general roles in neuronal development. This POWRE award will allow an excellent investigator with substantial teaching duties to begin a research project using new molecular methodology on a system and a question with in which she has had a long -standing interest.