Defining the patterns of gene expression in the developing human brain

October 2010

In the adult human brain, the cerebral hemispheres (or neocortex) are made up of multiple layers of cells and axon connections. The structural, physiological, and neurochemical properties of these layers varies between different regions in order to support unique functions – for example the cortical area processing visual information differs from the area controlling movement.  During development of the cerebrum – corticogenesis – cells express a number of regulatory genes in graded or restricted patterns in order to orchestrate the differential development that determines this regional specialisation.  Understanding how this cortical map is determined is important for understanding the process of normal brain development, how this may be disrupted – for example, by brain damage – and how it might be repaired – for example, by use of stem cells. In a new study led by Dr Gavin Clowry and Professor Susan Lindsay, human brain tissue was studied to determine the pattern of expression of a number of genes that are involved in the development and connections of the neurones that control movement (corticospinal motor neurons).  Human embryonic and foetal neocortical tissues from between 8 and 15 weeks post-conception were examined for three important regulatory genes (ROBO1, SRGAP1 and CTIP2) and the proteins they encode.  It was shown that these three markers were found mainly in the front of the brain (anterior neocortex) and that their co-expression marks the early location of the area of cortex that contains the main neurones that control movement - corticospinal projection neurones. The ability to identify this important area at an early stage of life and to know some of the genes that are expressed will allow the group to further study the processes that enable the brain to develop the important function of movement control. It may also give clues as to how to produce corticospinal motor neurones from stem cells which could have applications in helping develop treatments from stroke, cerebral palsy and motor neuron diseases.

The corticofugal neuron-associated genes ROBO1, SRGAP1, and CTIP2 exhibit an anterior to posterior gradient of expression in early fetal human neocortex development. Ip BK, Bayatti N, Howard NJ, Lindsay S, Clowry GJ (2010) Cerebral Cortex (Link to the article)

published on: 1st October 2010