This article reviews current knowledge on the origin and development of microglia as well as on regulatory factors that influence microglial development within the neural tube during embryogenesis. Ameboid microglia found in the developing neural tube originate from mesodermal precursors derived from the yolk sac. These microglial cells, which exhibit characteristic features of reactive microglia, undergo mitosis in situ in the nervous parenchyma and function as the full-blown phagocytes involved in the removal of cellular debris resulting from neural tube defect or normal cellular turnover. During embryogenesis, the microglia express various cytokines, growth factors and chemokines. Some of those factors together with other local factors may influence the proliferation and activation of microglia in the developing neural tube.

Prenatal exposure to teratogen agents is linked to the pathogenesis of neurodevelopment disorders, but the mechanisms leading to the neurodevelopmental disturbance are poorly understood. To elucidate this, an in vitro model of microglial activation induced by neuronal injury has been characterized. In this connection, exposure of primary microglial cells to the conditioned medium from the neuronal damage induced by teratogen, cyclophosphamide, is accompanied by a reactive microgliosis as assessed by reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, lectin histochemistry, double labeling immunohistochemistry and in situ hybridization. Our results showed that reactive microglia were capable of releasing various cytokines such as tumor necrosis factor-K, interleukin-1, interleukin-6, transforming growth factor-L and nitric oxide. Also, we have shown that macrophage colony-stimulating factor (M-CSF) was in fact produced by the reactive microglia. Concomitant to this was the increased expression of M-CSF receptor in these cells following the teratogen-induced neuronal injury. The up-regulation of M-CSF receptor suggests that the cells are capable of responding to self-derived M-CSF in an autocrine fashion. Results with antibody neutralization further suggest that microglial proin