Proliferation and Differentiation Deficits are a Major Convergence Point for Neurodevelopmental Disorders

Carl Ernst

doi:10.1016/j.tins.2016.03.001

Proliferation and Differentiation Deficits are a Major Convergence Point for Neurodevelopmental Disorders

Trends Neurosci. 2016 May;39(5):290-299. doi: 10.1016/j.tins.2016.03.001. Epub 2016 Mar 28.

Author

Carl Ernst¹

Affiliation

¹ 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.

PMID: 27032601
DOI: 10.1016/j.tins.2016.03.001

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.

Keywords: cancer; differentiation; induced pluripotent stem cell; macrocephaly; microcephaly; neural stem cells; neurodevelopmental disorders; proliferation.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation / physiology*
Cell Proliferation / physiology*
Humans
Neural Stem Cells / cytology*
Neurodevelopmental Disorders / genetics
Neurodevelopmental Disorders / pathology*