| Autor: |
Messaoudi, S., Stoufflet, J., Fouquet, C., Doulazmi, M., Allam, A., Paillard, T., Trembleau, A., Caillé, I. |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
bioRxiv |
| Popis: |
The Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability, and the first monogenic cause of Autism Spectrum Disorder. FXS is caused by the absence of the RNA-binding protein FMRP (Fragile X Mental Retardation Protein). Neuronal migration is an essential step of brain development allowing displacement of neurons from their germinal niches to their final integration site. The role of FMRP in tangential neuronal migration remains unexplored. We studied the consequences of FMRP absence on tangential migration, using the postnatal Rostral Migratory Stream (RMS) as an experimental system. In Fmr1-null RMS, neurons exhibit a slowed-down migration and an impaired trajectory, associated with defects of their centrosomal movement. Through RNA-interference-induced knock-down of Fmr1 , we show that these migratory defects are cell-autonomous. Mutated neurons also display altered morphology as well as defects in their microtubule tyrosination distribution. Finally, we show that the FMRP mRNA target involved in these defects is MAP1B (Microtubule-Associated Protein 1B), whose knock-down rescues most migratory defects. Our results thus unveil a new neurodevelopmental role of FMRP, as a crucial actor of postnatal tangential migration, potentially important for the understanding of FXS pathophysiology. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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