The Application of Differential Display to the Brain: Adaptations for the Study of Heterogeneous Tissue

One of the main advantages of using differential display is the ability to examine simultaneously gene expression in multiple mRNA populations. In other techniques, such as differential screening or subtractive hybridization, only two mRNA populations can be easily examined at the same time. This feature is of particular importance in identifying specific changes in gene expression within a complex biological system. It has been estimated that at least 30% and perhaps as many as 50% of all mammalian genes code for proteins that are uniquely expressed in the brain (1 ), In addition, with the possible exception of the immune system, the brain is the most heterogeneous tissue in the body. Therefore, the analysis of alterations in gene expression in the brain is complicated by the complexity of the message population and the heterogeneity of tissues within the brain. The differential display technique as originally described (2 ) was developed and proven on homogenous cell lines and many of the applications have been specific to homogenous cell lines. However, a limited amount of work had been done assessing the utility of differential display analysis in heterogeneous tissues and in particular the analysis of complex physiological changes within an in vivo biological system.