The versatility of RhoA activities in neural differentiation
| Autor: | Arie Horowitz, Lorraine Iacovitti, Jingli Cai, Junning Yang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Genetically modified mouse
RHOA Neurogenesis Retinoic acid Biology Bone morphogenetic protein Biochemistry Smad1 Protein 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Humans Noggin Embryonic Stem Cells 030304 developmental biology 0303 health sciences Cell Biology Embryonic stem cell Cell biology chemistry 030220 oncology & carcinogenesis biology.protein Commentary - Commissioned Guanine nucleotide exchange factor Signal transduction Carrier Proteins rhoA GTP-Binding Protein |
| Zdroj: | Small GTPases. 10:26-32 |
| ISSN: | 2154-1256 2154-1248 |
| DOI: | 10.1080/21541248.2016.1273171 |
| Popis: | In this commentary we discuss a paper we published recently on the activities of the GTPase RhoA during neural differentiation of murine embryonic stem cells, and relate our findings to previous studies. We narrate how we found that RhoA impedes neural differentiation by inhibiting the production as well as the secretion of noggin, a soluble factor that antagonizes bone morphogenetic protein. We discuss how the questions we tried to address shaped the study, and how embryonic stem cells isolated from a genetically modified mouse model devoid of Syx, a RhoA-specific guanine exchange factor, were used to address them. We detail several signaling pathways downstream of RhoA that are hindered by the absence of Syx, and obstructed by retinoic acid, resulting in an increase of noggin production; we explain how the lower RhoA activity and, consequently, the sparser peri-junctional stress fibers in Syx−/− cells facilitated noggin secretion; and we report unpublished results showing that pharmacological inhibition of RhoA accelerates the neuronal differentiation of human embryonic stem cells. Finally, we identify signaling mechanisms in our recent study that warrant further study, and speculate on the possibility of manipulating RhoA signaling in combination with other pathways to drive the differentiation of neuronal subtypes. |
| Databáze: | OpenAIRE |
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