FMRP regulates multipolar to bipolar transition affecting neuronal migration and cortical circuitry.

Détails

ID Serval
serval:BIB_1A1E1BA2727C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
FMRP regulates multipolar to bipolar transition affecting neuronal migration and cortical circuitry.
Périodique
Nature neuroscience
Auteur⸱e⸱s
La Fata G., Gärtner A., Domínguez-Iturza N., Dresselaers T., Dawitz J., Poorthuis R.B., Averna M., Himmelreich U., Meredith R.M., Achsel T., Dotti C.G., Bagni C.
ISSN
1546-1726 (Electronic)
ISSN-L
1097-6256
Statut éditorial
Publié
Date de publication
12/2014
Volume
17
Numéro
12
Pages
1693-1700
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Deficiencies in fragile X mental retardation protein (FMRP) are the most common cause of inherited intellectual disability, fragile X syndrome (FXS), with symptoms manifesting during infancy and early childhood. Using a mouse model for FXS, we found that Fmrp regulates the positioning of neurons in the cortical plate during embryonic development, affecting their multipolar-to-bipolar transition (MBT). We identified N-cadherin, which is crucial for MBT, as an Fmrp-regulated target in embryonic brain. Furthermore, spontaneous network activity and high-resolution brain imaging revealed defects in the establishment of neuronal networks at very early developmental stages, further confirmed by an unbalanced excitatory and inhibitory network. Finally, reintroduction of Fmrp or N-cadherin in the embryo normalized early postnatal neuron activity. Our findings highlight the critical role of Fmrp in the developing cerebral cortex and might explain some of the clinical features observed in patients with FXS, such as alterations in synaptic communication and neuronal network connectivity.

Mots-clé
Animals, Cell Movement/physiology, Cell Polarity/physiology, Female, Fragile X Mental Retardation Protein/physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Nerve Net/cytology, Nerve Net/physiology, Neurons/physiology, Organ Culture Techniques, Pregnancy, Somatosensory Cortex/cytology, Somatosensory Cortex/physiology
Pubmed
Création de la notice
06/03/2017 18:23
Dernière modification de la notice
20/08/2019 13:51
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