Bethyl Laboratories, Inc.

Overview

Brain size and cognitive ability sets humans apart from their closest evolutionary relatives. It is suggested that the phenomenon of encephalization in hominids may have involved gain-of-function changes in genes that have been associated with microcephalic disorders. Primary microcephaly, Seckel syndrome, and microcephalic osteodysplastic primordial dwarfism type II (MOPDII) are disorders that exhibit microcephaly, a human neurodevelopmental disorder characterized by reduced brain size. Microcephalic brains show loss of cellularity but near-to-normal architecture which strengthens the assertion that the associated genes may be responsible for the increase in human brain size through evolution. The genes associated with primary microcephaly include MCPH1, MCPH2, MCPH3/CDK5RAP2, MCPH4, MCPH5/ASPM, MCPH6/CENPJ, and MCPH7/SIL. Mutations in ATR and pericentrin have been shown to be the cause of Seckel syndrome and MOPDII, respectively. The products of some of the MCPH genes and the pericentrin gene have been localized to the centrosome and mitotic spindle. At the cellular level, these proteins play roles in the DNA damage response, the regulation of cell cycle progression, checkpoint regulation, and proliferation capacity. The exact role of these genes in neurogenesis is still not clear, and further studies of this group of proteins are required to assess their biological functions as well as provide insight into their role in hominid encephalization.

Selected Review
1. G. K. Thornton and C. G. Woods, "Primary Microcephaly: Do All Roads Lead to Rome?," Trends Genet. 25, no. 11 (2009): 501-510.
2. B. Delaval and S. J. Doxsey, "Pericentrin in Cellular Function and Disease," J Cell Biol. 188, no. 2 (2010): 181-190.