Genetic targeting of microglia

Genetic targeting of microglia and other myeloid cells in the central nervous system (CNS) is highly desirable as they are critical effectors and regulators of changes in CNS homeostasis during development as well as in health and disease. Therefore, genetic reprogramming of microglia could constitute a central approach for potentially reducing disease burden. Previous attempts to target only microglia in vivo failed because of the similarities to their hematopoietic relatives in the circulation. However, this concept has been challenged by recent results of developmental and gene expression profiling studies which used novel molecular biological tools to unravel the origin of microglia and to define their role as specialized tissue macrophages clearly distinct from monocytes or monocyte-derived macrophages. The aim of this review is to recapitulate the history of microglia targeting approaches and finally highlight recent achievements in the field. We will discuss the pros and cons of the newly available genetic tools, their potential for future microglia research and genetic strategies.