Biology subjects

Roussat, M.

Publications and source records attributed to Roussat, M..

3 recordsLinked to original sources

bioRxiv2025

Shared and distinct neural signatures of inhibitory control deficits in attention-deficit/hyperactivity disorder and autism

BackgroundAttention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share deficits in inhibitory control, yet direct comparisons of their neurobiological underpinnings remain sparse and are often confounded by comorbidity. We examined shared and distinct abnormalities in brain activation and circuit connectivity associated with inhibitory control in non-comorbid ADHD and ASD. MethodsBrain activity and hyperdirect pathway connectivity during inhibitory control were examined in children with non-comorbid ADHD (age: 11.1{+/-}0.24y) and children with non-comorbid ASD (age: 11.1{+/-}0.39y), compared with typically developing (TD) children (age: 10.9{+/-}0.09y), and benchmarked against healthy adults (age: 24.1{+/-}1.26y), using fMRI stop-signal task data. ResultsBoth ADHD and ASD groups showed reduced activation in salience and frontoparietal network regions alongside increased activation in default mode network (DMN) regions, consistent with triple-network dysfunction. These activation deficits were more pronounced in ASD, whose activation profile also diverged most from adults. At the circuit level, only ASD showed abnormal hyperdirect connectivity, involving insula-STN and preSMA-STN pathways and further reflected in a composite insula/IFG-STN connectivity measure, indicating broader cortical-STN disruption. Importantly, across all children, reduced salience/frontoparietal relative to DMN engagement correlated with greater parent-reported inhibitory control deficits, and in ASD, individual differences in insula/IFG-STN connectivity showed the same association, highlighting the behavioral relevance of both network- and circuit-level abnormalities. ConclusionsADHD and ASD share network-level but differ in circuit-level abnormalities underlying inhibitory control deficits. Together, these insights advance the neurobiology of inhibitory control in ADHD and ASD and provide potential targets for neuroscience-informed interventions addressing both shared and disorder-specific mechanisms.

neuroscience↗

bioRxiv2021

Control of G2 phase duration by CDC25B modulates the switch from direct to indirect neurogenesis in the neocortex

During development, cortical neurons are produced in a temporally regulated sequence from apical progenitors, directly, or indirectly through the production of intermediate basal progenitors. The balance between these major progenitors types is determinant for the production of the proper number and types of neurons and it is thus important to decipher the cellular and molecular cues controlling this equilibrium. Here we address the role of a cell cycle regulator, the CDC25B phosphatase, in this process. We show that deleting CDC25B in apical progenitors leads to a transient increase of the production of TBR1+ neurons at the expense of TBR2+ basal progenitors in mouse neocortex. This phenotype is associated with lengthening of the G2 phase of the cell cycle, the total cell cycle length being unaffected. Using in utero electroporation and cortical slice cultures, we demonstrate that the defect in TBR2+ basal progenitor production requires interaction with CDK1 and is due to the G2 phase lengthening in CDC25B mutants. Altogether, this study identifies a new role for CDC25B and the length of the G2 phase in direct versus indirect neurogenesis at early stages of the cortical development.

developmental biology↗

bioRxiv2017

Neurogenic decisions require a cell cycle independent function of the CD25B phosphatase

A fundamental issue in developmental biology and in organ homeostasis is understanding the molecular mechanisms governing the balance between stem cell maintenance and differentiation into a specific lineage. Accumulating data suggest that cell cycle dynamics plays a major role in the regulation of this balance. Here we show that the G2/M cell cycle regulator CDC25B phosphatase is required in mammals to finely tune neuronal production in the neural tube. We show that in chick neural progenitors, CDC25B activity is both required and sufficient to stimulate neurogenic divisions and to promote neuronal differentiation. We design a mathematical model showing that within a limited period of time, cell cycle length modifications cannot account for changes in the ratio of the mode of division. Using a CDC25B point mutation that cannot interact with CDK, we show that part of CDC25B activity on neurogenic divisions is independent of its action on the cell cycle.

developmental biology↗