Genetic ablation of the Rho GTPase Rnd3 triggers developmental defects in internal capsule and the globus pallidus formation
| Autor: | Carme Espinet, Begoña Ballester-Lurbe, Catherine Fleitas, Pau Marfull-Oromí, Daniel Rocandio, Ignacio Pérez-Roger, José Terrado, Joaquim Egea, Bahira Zammou |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Nervous system rho GTP-Binding Proteins Internal capsule Thalamus Striatum Biology Globus Pallidus Biochemistry 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Internal Capsule Neural Pathways medicine Animals Brain Chemistry Mice Knockout Median Eminence Brain Gene Expression Regulation Developmental Axons Mice Inbred C57BL Neostriatum 030104 developmental biology medicine.anatomical_structure Globus pallidus nervous system Cerebral cortex Forebrain Axon guidance Neuroscience 030217 neurology & neurosurgery Gene Deletion |
| Zdroj: | Journal of neurochemistryReferences. 158(2) |
| ISSN: | 1471-4159 |
| Popis: | The forebrain includes the cerebral cortex, the thalamus, and the striatum and globus pallidus (GP) in the subpallium. The formation of these structures and their interconnections by specific axonal tracts take place in a precise and orchestrated time and spatial-dependent manner during development. However, the knowledge of the molecular and cellular mechanisms that are involved is rather limited. Moreover, while many extracellular cues and specific receptors have been shown to play a role in different aspects of nervous system development, including neuron migration and axon guidance, examples of intracellular signaling effectors involved in these processes are sparse. In the present work, we have shown that the atypical RhoGTPase, Rnd3, is expressed very early during brain development and keeps a dynamic expression in several brain regions including the cortex, the thalamus, and the subpallium. By using a gene-trap allele (Rnd3gt ) and immunological techniques, we have shown that Rnd3gt/gt embryos display severe defects in striatal and thalamocortical axonal projections (SAs and TCAs, respectively) and defects in GP formation already at early stages. Surprisingly, the corridor, an important intermediate target for TCAs is still present in these mutants. Mechanistically, a conditional genetic deletion approach revealed that Rnd3 is primarily required for the normal development of Medial Ganglionic Eminence-derived structures, such as the GP, and therefore acts non-cell autonomously in SAs and TCAs. In conclusion, we have demonstrated the important role of Rnd3 as an early regulator of subpallium development in vivo and revealed new insights about SAs and TCAs development. |
| Databáze: | OpenAIRE |
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