Developmental regulation of the thalamus by LIM homeodomain transcription factor Isl1
| Autor: | Jing-Ruei Lin, 林敬睿 |
|---|---|
| Rok vydání: | 2015 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 103 The present study is focused on investigation of the function of LIM-homeodomain transcription factor Isl1 in developing mouse thalamus. The thalamus is the nucleus for relaying the sensory information to cerebral cortex. Isl1 is expressed in the thalamic reticular nucleus, corridor cells region and striatum which are intermediate targets for thalamocortical axonal projections. We studied the formation of thalamocortical axonal projections in Nestin-Cre;Isl1fl/fl knockout mouse brain, and the roles of Isl1 in developmental regulation of the corridor cells region and thalamic reticular nucleus. We found that, in E15.5 Nestin-Cre;Isl1fl/fl knockout mice, some thalamocortical axons abnormally extended toward the ventral telencephalon, though other thalamocortical axons were navigated through the ventral MGE to the cortical regions, but did not reach the pallium-subpallium boundary. We further investigated the constitution of corridor cells region in E13.5 Nestin-Cre; Isl1fl/fl knockout mice. Loosely distribution of corridor cells which were immunoreactive for Nolz-1 was observed, and Nolz-1 immunoreactive cells were increased in the locus of globus pallidus. These findings suggested the possibility that the constitution of corridor cells region was abnormally spreaded into the ventral MGE in the absence of Isl1, which might lead to the misrouted thalamocortical projections. We also studied development of the thalamic reticular nucleus in the ventral thalamus. We found aberrant development of thalamic reticular nucleus without the abnormal cell apoptosis or proliferation in E15.5 Nestin-Cre; Isl1fl/fl knockout mice as evidenced by no significant changes in the number of TUNEL and activated caspase 3-positive apoptotic cells and Ki67- and phspho-histone 3-positive proliferating cells. Furthermore, in control mice, Lim1/2 and Foxp1 immunoreactivity were expressed in the ventral lateral geniculate nucleus of ventral thalamus, but not in the thalamic reticular nucleus. In contrast, Lim1/2 and Foxp1 were ectopically expressed in the thalamic reticular nucleus of E15.5 Nestin-Cre; Isl1fl/fl knockout mice. These results suggested that the cell identity of thalamic reticular nucleus might be respecified toward the cell identity of neighboring ventral lateral geniculate nucleus. Because cells in the thalamic reticular nucleus and its neighboring ventral lateral geniculate nucleus and zona incerta express different LIM homeodomain transcription factors, our study raises the possibility that the cell fate and differentiation of different thalamic nuclei are determined by the LIM codes as originally proposed in development of neurons in the spinal cord. In summary, our present study implicates a role of Isl1 in maintaining the proper constitution and organization of the corridor cells region, and further suggests a role of Isl1 in developmental regulation of neuronal subtypes in the ventral thalamus. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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