Systems biology: transforming our understanding of disease

Greener, Mark

doi:10.1002/psb.1634

Cited by 1 publication

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“…Advancements in such systems biology techniques is an exciting field as it integrates different types of data to create a more complete representation of human biology. This new modelling method has also improved drug development and diagnostic rates across several disease states (Greener, 2017).…”

Section: Interconnected Pathways In Neurodevelopmental Disordersmentioning

confidence: 99%

Molecular mechanisms underlying malformations of cortical development

Oishi¹

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Nuclear Factor One X (NFIX) haploinsufficiency in humans results in Malan syndrome, a disorder characterized by overgrowth, macrocephaly and intellectual disability. Although clinical assessments have determined the underlying symptomology of Malan syndrome, the fundamental mechanisms contributing to the enlarged head circumference and intellectual disability in these patients remains undefined. Here, we used Nfix heterozygous mice as a model to investigate these aspects of Malan syndrome. Volumetric magnetic resonance imaging (MRI) was used to calculate the volumes of 20 brain sub regions. Diffusion tensor MRI was used to perform tractography-based analyses of the corpus callosum, hippocampal commissure, and anterior commissure, as well as structural connectome mapping of the whole brain. Immunohistochemistry examined the neocortical cellular populations. Two behavioural assays were performed, including the active place avoidance task to assess spatial navigation and learning and memory function, and the 3-chambered sociability task to examine social behaviour. Adult Nfix+/-mice exhibit significantly increased brain volume (megalencephaly) compared to wildtypes, with the cerebral cortex showing the highest increase. Moreover, all three forebrain commissures, in particular the anterior commissure, revealed significantly reduced fractional anisotropy, axial and radial diffusivity, and tract density intensity. Structural connectome analyses revealed aberrant connectivity between many crucial brain regions. Finally, Nfix+/-mice exhibit behavioural deficits that model intellectual disability. Collectively, these data provide a significant conceptual advance in our understanding of Malan syndrome by suggesting that megalencephaly underlies the enlarged head size of these patients, and that disrupted cortical connectivity may contribute to the intellectual disability these patients exhibit.

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Section: Interconnected Pathways In Neurodevelopmental Disordersmentioning

confidence: 99%

Molecular mechanisms underlying malformations of cortical development

Oishi¹

View full text Add to dashboard Cite

show abstract

Systems biology: transforming our understanding of disease

Cited by 1 publication

References 7 publications

Molecular mechanisms underlying malformations of cortical development

Molecular mechanisms underlying malformations of cortical development

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