title: Proliferation and Differentiation Deficits are a Major Convergence Point for Neurodevelopmental Disorders.
abstract: Several lines of evidence suggest that proliferation and differentiation in neural stem cells (NSCs) are a major convergence point of neurodevelopmental disorders (NDDs). Most genes with truncating mutations are implicated in NSC proliferation and differentiation (e.g., MBD5, CDKL5, and MECP2). Similarly, reciprocal deletion/duplication copy-number variants (CNVs), such as 1q21.1 and 16p11.2, are inversely correlated with head size. In addition, pathways such as MAPK, mTOR, and RAS, which are important in cancer, a disease of uncontrolled cell proliferation, are implicated in NDDs. These deficits are a measurable output of patient-derived induced neural progenitor cells, and may represent a diagnostic tool and a possible clinical intervention point for molecular therapies, irrespective of genotype.
authors.affiliation: Department of Psychiatry, McGill University, Montreal, QC, Canada; Department of Human Genetics, McGill University, Montreal, QC, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada; McGill Group for Suicide Studies, Douglas Hospital Research Institute, Montreal, QC, Canada. Electronic address: carl.ernst@mcgill.ca.
authors.forename: Carl
authors.initials: C
authors.lastname: Ernst
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology*; D065886:Neurodevelopmental Disorders / Q000235:genetics / Q000473:pathology*
keywords: cancer; differentiation; induced pluripotent stem cell; macrocephaly; microcephaly; neural stem cells; neurodevelopmental disorders; proliferation