Newcastle University

The Wellcome Trust/MRC Human Developmental Biology Resource, jointly maintained by Newcastle University and University College London, provides a valuable bank of embryonic and fetal human brains allowing investigation of brain development.  This includes studies of the expression of genes that control processes such as functional specialisation of different areas (arealisation) and the increase in the number of neurones (neurogenesis), and allows important comparisons between human development and what we have learnt from studies of rodents.

In this study Dr Gavin Clowry, Professor Susan Lindsay and colleagues investigated the critical period of development from the formation of the cells destined to become the cerebral cortex (cortical plate) to the arrival of the major inputs (thalamocortical afferents). They conducted this in much greater detail than any previous study, allowing them to identify with accuracy the various compartments of the developing cortex.

In performing this analysis they made a number of important and novel observations. For instance, the cell layer called the subplate, into which neuronal inputs grow and then wait for a period before continuing into the cortex, was shown to be a distinct differentiated layer by 10 weeks post-conception, and the expression of two genes (synaptophysin and vesicular GABA transporter) indicated the existence of a spontaneously active synaptic network even before the arrival of the thalamocortical afferents. This observation has already been cited by Bystron, Blakemore and Rakic (Nature Rev Neurosci 2008 9:110-122) in their recent revision of the Boulder Committee agreement on the naming of the compartments of the developing human brain.

Another major observation was the complexity of the proliferating layers in comparison to rodents.  In humans, a large area called the subventricular zone includes an outer layer that was shown to contain a reservoir of precursor cells expressing the gene PAX6 which are normally confined to the ventricular zone in rodents. Further dissection of the molecular and functional anatomy of this important area of the developing brain should give clues to origins of the rapid evolution in size and complexity of the human neocortex.

A molecular neuroanatomical study of the developing human neocortex from 8 to 17 postconceptional weeks revealing the early differentiation of the subplate and subventricular zone.  Bayatti N, Moss JA, Sun L, Ambrose P, Ward JFH, Lindsay S, Clowry GJ (2008) Cerebral Cortex  18:1536-1548. (PubMed abstract: http://www.ncbi.nlm.nih.gov/pubmed/17965125)