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Billuart, P.

Publications and source records attributed to Billuart, P..

2 recordsLinked to original sources

Astrocytes close the critical period for visual plasticity

Summary paragraphBrain postnatal development is characterized by critical periods of experience-dependent remodeling1,2. Termination of these periods of intense plasticity is associated with settling of neuronal circuits, allowing for efficient information processing3. Failure to end critical periods thus results in neurodevelopmental disorders4,5. Yet, the cellular processes defining the timing of these developmental periods remain unclear. Here we show in the mouse visual cortex that astrocytes control the closure of the critical period. We uncover a novel underlying pathway involving regulation of the extracellular matrix that allows interneurons maturation via an unconventional astroglial connexin signaling. We find that timing of the critical period closure is controlled by a marked developmental upregulation of the astroglial protein connexin 30 that inhibits expression of the matrix degrading enzyme MMP9 through the RhoA-GTPase signaling pathway. Our results thus demonstrate that astrocytes not only influence activity and plasticity of single synapses, but are also key elements in the experience-dependent wiring of brain developing circuits. This work, by revealing that astrocytes promote the maturation of inhibitory circuits, hence provide a new cellular target to alleviate malfunctions associated to impaired closure of critical periods.

neuroscience↗

A Point Mutation in the RNA Recognition Motif of CSTF2 Associated with Intellectual Disability in Humans Causes Defects in 3' End Processing

CSTF2 encodes an RNA-binding protein that is essential for mRNA cleavage and polyadenylation (C/P). No disease-associated mutations have been described for this gene. Here, we report a mutation in the RNA recognition motif (RRM) of CSTF2 that changes an aspartic acid at position 50 to alanine (p.D50A), resulting in intellectual disability in male patients. In mice, this mutation was sufficient to alter polyadenylation sites in over 1,000 genes critical for brain development. Using a reporter gene assay, we demonstrated that C/P efficiency of CSTF2D50A was lower than wild type. To account for this, we determined that p.D50A changed locations of amino acid side chains altering RNA binding sites in the RRM. The changes modified the electrostatic potential of the RRM leading to a greater affinity for RNA. These results highlight the importance of 3' end mRNA processing in correct expression of genes important for brain plasticity and neuronal development.

molecular biology↗