The long-term aim of this work is to create an Electronic Atlas of the Developing Human Brain (EADHB) which will have two major components:

1. A Digital Atlas comprising:

• Computer based 3-D reconstructions, either Optical Projection Tomography (OPT) models or reconstructions based on stained sections, (Histology Resolution Models).
  
• Anatomical annotations of the 3-D reconstructions linked to an anatomical database.
  

2. A Gene Expression Database comprising:

• High resolution gene-expression data mapped onto the 3-D reconstructions
  

There are 5 specific aims in the pilot NIH-funded project which is being conducted in the 2000-2003 period:

1. Create 3-D computer based reconstructions of the human brain at different stages of development.

2. Define high resolution expression patterns for selected brain gene markers and map these to the corresponding 3-D reconstructions.

3. Test the 3-D reconstructions and gene expression mapping.

4. Create a prototype database and address interoparability.

5. Test the application of the prototype gene expression database.

In the future, the EADHB aims to provide the wider scientific and medical communities with a dynamic tool for documenting and analyzing gene expression patterns and morphological changes in the developing human brain.

The human brain develops initially from a simple tube to a complex, highly organised structure with unique cognitive functions, although the details of this process are poorly understood. In part, this is due to inherent limitations of anatomical approaches, (quite large parts of the brain appear to be rather featureless when analyzed using histological stains). In addition, our knowledge of the three-dimensional (3-D) structure of the developing brain has been extremely limited. Underlying the major changes that occur as the brain develops are genes. It is when and where they are switched on and off, and how their products function and interact with each other and with the environment, that drives brain development.

We are conducting pioneering studies of gene expression in early development and developing computer programs to generate 3-D electronic images of the brain at different stages of development. The 3-D images for each developmental stage provide templates onto which we can map gene expression patterns and also anatomical features, providing a powerful means of defining and comparing the patterns of activity of large numbers of different genes. Using a similar approach to the Mouse Atlas and Gene Expression Database Project, our aim is to develop an electronic database into which other laboratories can input data on gene expression in the developing brain and to search the database. The expression data will be linked to an anatomical database and to gene expression/anatomical databases of the mouse and other model organisms.