Mapping Genes that Modulate Mouse Brain Development: A Quantitative Genetic Approach

Abstract

The complexity of CNS development is staggering. In mice a total of approximately 75 million neurons and 25 million glial cells are generated, moved, connected, and integrated into hundreds of different circuits over a period of 1 month. The process is coordinated by the expression of a large fraction of the genome — as many as 40 000 genes are involved (Sutcliffe 1988; Adams et al. 1993). These same genes coordinate the development of the human brain, but a thousand times more neurons are generated (Williams and Herrup 1988) and their integration and training take more than a decade. While 5000 of these genes have common roles in cellular metabolism, this still leaves a huge complement that have selective, transient, and partially redundant roles in the development of different parts of the brain (Usui et al. 1994; Gautvik et al. 1996). Reductionist approaches that focus on isolated processes and molecules may seem hopelessly inadequate, but they are an absolute necessity at this early stage of analysis and understanding.

In my opinion there are only quantitative differences, not qualitative differences, between the brain of a man and that of a mouse. (Ramón y Cajal 1890)

The difference in behavioral capacity between man and chimpanzee may be no more than the addition of one cell generation in the segmentation of the neuroblasts which form the cerebral network. (Lashley 1949)