Qr: author:"Tomohiro Doura"
Showing 1 - 2 of 2 results
1.
Light- and chemical-induced ciliary signaling governs dorsal/ventral regionalization of human telencephalic organoids.
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Shimada, IS
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Goto, A
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Hashimoto, Y
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Inoue, H
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Sugawara, T
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Doura, T
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Fujita, T
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Iwata, T
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Shimmoto, R
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Takase, H
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Itoh, M
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Kiyonaka, S
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Kato, Y
Abstract:
Neural stem/progenitor cells (NPCs) have primary cilia, which are critical organelles for Sonic hedgehog signaling. However, little is known about the components of primary cilia in NPCs and whether manipulating signaling in the cilia is sufficient to alter dorsal/ventral regional identity. Using a human telencephalic organoid model, we perform comprehensive proteomic profiling of NPC cilia and find enrichment in GTPase signaling. Deletion of the ciliary GTPase ARL13B reduces ciliary localization of GPR161, an orphan G protein-coupled receptor 161 that negatively regulates Sonic hedgehog, resulting in ventralization of NPCs. GPR161 deletion also induces ventralization. To investigate whether manipulation of ciliary signaling is sufficient to restore dorsal identity in this context, we optogenetically elevate ciliary cAMP, rescuing dorsal fate in GPR161 KO organoids. Furthermore, chemogenetic induction of GPR161 removal from cilia is sufficient to increase ventral NPCs. These data indicate that ciliary signaling functions as a critical switch regulating dorsal/ventral fate decisions.
2.
Chemogenetics of cell surface receptors: beyond genetic and pharmacological approaches.
Abstract:
Cell surface receptors transmit extracellular information into cells. Spatiotemporal regulation of receptor signaling is crucial for cellular functions, and dysregulation of signaling causes various diseases. Thus, it is highly desired to control receptor functions with high spatial and/or temporal resolution. Conventionally, genetic engineering or chemical ligands have been used to control receptor functions in cells. As the alternative, chemogenetics has been proposed, in which target proteins are genetically engineered to interact with a designed chemical partner with high selectivity. The engineered receptor dissects the function of one receptor member among a highly homologous receptor family in a cell-specific manner. Notably, some chemogenetic strategies have been used to reveal the receptor signaling of target cells in living animals. In this review, we summarize the developing chemogenetic methods of transmembrane receptors for cell-specific regulation of receptor signaling. We also discuss the prospects of chemogenetics for clinical applications.
