January 05, 2022
Volume 110, Issue 1
Brain ventricles as windows into brain development and disease
Dilation of the fluid-filled cerebral ventricles (ventriculomegaly) characterizes hydrocephalus and is frequently seen in autism and schizophrenia. Recent work suggests that the genomic study of congenital hydrocephalus may be unexpectedly fertile ground for revealing insights into neural stem cell regulation, human cerebrocortical development, and pathogenesis of neuropsychiatric disease.
February 01, 2022
Volume 24, Issue 2
Variants in ADD1 cause intellectual disability, corpus callosum dysgenesis, and ventriculomegaly in humans
Adducins interconnect spectrin and actin filaments to form polygonal scaffolds beneath the cell membranes and form ring-like structures in neuronal axons. Adducins regulate mouse neural development, but their function in the human brain is unknown. We used exome sequencing to uncover ADD1 variants associated with intellectual disability (ID) and brain malformations. We studied ADD1 splice isoforms in mouse and human neocortex development with RNA sequencing, super resolution imaging, and immunoblotting...
April 04, 2022
Volume 25, Issue 4
Impaired neurogenesis alters brain biomechanics in a neuroprogenitor- based genetic subtype of congenital hydrocephalus
Hydrocephalus, characterized by cerebral ventricular dilatation, is routinely attributed to primary defects in cerebrospinal fluid (CSF) homeostasis. This fosters CSF shunting as the leading reason for brain surgery in children despite considerable disease heterogeneity. In this study, by integrating human brain transcriptomics with whole-exome sequencing of 483 patients with congenital hydrocephalus (CH), we found convergence of CH risk genes in embryonic neuroepithelial stem cells. Of all CH risk genes, TRIM71/lin-41...