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Non-Invasive Modulation and Robotic Mapping of Motor Cortex in the Developing Brain
Published on: July 1, 2019
MicroRNA-129 modulates neuronal migration by targeting Fmr1 in the developing mouse cortex
Chao Wu1, Xiaoling Zhang1, Pan Chen1
1The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primates Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 100005, Beijing, China.
Abstract:
During cortical development, neuronal migration is one of the most important steps for normal cortical formation and function, and defects in this process cause many brain diseases. However, the molecular mechanisms underlying this process remain largely unknown. In this study, we found that miR-129-5p and miR-129-3p were expressed in both neural progenitor cells and cortical neurons in the developing murine cortex. Moreover, abnormal miR-129 expression could block radial migration of both the deeper layer and upper layer neurons, and impair the multipolar to bipolar transition. However, antagomir-mediated inhibition resulted in overmigration of neurons. In addition, we showed that Fragile X Mental Retardation gene 1 (Fmr1), which is mutated in the autism spectrum disorder fragile X syndrome, is an important regulatory target for miR-129-5p. Furthermore, Fmr1 loss-of-function and gain-of-function experiments showed opposite effects on miR-129 regulation of neuronal migration, and restoring Fmr1 expression could counteract the deleterious effect of miR-129 on neuronal migration. Taken together, our results suggest that miR-129-5p could modulate the expression of fragile X mental retardation 1 protein (FMRP) to ensure normal neuron positioning in the developing cerebral cortex.
Insights
MicroRNAs miR-129-5p and miR-129-3p are crucial for normal neuronal migration during brain development. Dysregulation of miR-129 impacts neuron positioning and is linked to Fragile X syndrome via Fmr1 regulation.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Neuronal migration is essential for proper brain formation and function.
- Defects in neuronal migration are linked to various neurological disorders.
- The molecular mechanisms governing neuronal migration are not fully understood.
Purpose of the Study:
- To investigate the role of miR-129 in neuronal migration during cortical development.
- To identify molecular targets of miR-129 involved in neuronal positioning.
- To explore the connection between miR-129, Fmr1, and neurodevelopmental disorders.
Main Methods:
- Expression analysis of miR-129 in developing murine cortex.
- In vivo manipulation of miR-129 levels using antagomirs.
- Assessment of neuronal migration and cell transition dynamics.
- Fmr1 loss-of-function and gain-of-function studies.
- Analysis of FMRP expression in relation to miR-129.
Main Results:
- miR-129-5p and miR-129-3p are expressed in neural progenitor cells and cortical neurons.
- Altered miR-129 expression disrupts radial migration and multipolar-to-bipolar transition.
- Inhibition of miR-129 leads to neuronal overmigration.
- Fmr1 is a direct regulatory target of miR-129-5p.
- Fmr1 expression levels inversely affect miR-129's regulation of neuronal migration.
Conclusions:
- miR-129-5p regulates neuronal positioning by modulating FMRP levels.
- This miR-129-FMRP axis is critical for ensuring normal neuron placement in the developing cortex.
- Findings provide insights into molecular mechanisms underlying neurodevelopmental disorders like Fragile X syndrome.
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