The origin of microglial precursors is a controversial issue with two camps claiming distinct origins.

1. Microglial cells are of mesodermal origin.

2. Microglial cells originate from neuroepithelial cells.

The first view is supported by the majority of researchers, who believe that microglia derive either from monocytes that leave the blood and colonize the nervous parenchyma or from primitive hemipoietic cells (stem cells) that differentiate into microglia within the CNS. The evidence for each group can be summarized as follows. Evidence that microglial cells are of mesodermal origin is based on the fact that microglial cells and cells of monocytic lineage share common features, including the enzymes nucleoside diphosphatase, nonspecific esterase, and acid phosphatase. Additionally, both cell types contain vault particles and are labeled by several lectins. Antibodies have been developed that recognize both cell types in a variety of species. Ink- or carbon-labeled monocytes injected into the blood stream of newborn rats are incorporated into ramified microglia in adult animals, suggesting that microglia originate from monocytes that enter the nervous parenchyma via the blood stream. These findings together with the similarity of function of microglia and monocytic cells suggest a common origin. Less convincing evidence is that cells with morphological properties and patterns of membrane currents similar to those of microglia are derived from monocytes.

However, some authors maintain that at least some microglial cells are of neuroectodermal origin. Autoradiographic studies indicate that microglia are derived from glioblasts that also produce astrocytes, indicating that proliferating glioblasts form microglia. Microglial cells are found within the matrix cell layer during development, but these cells may be merely crossing the neuroepithelial layer after entering the nervous parenchyma and may not be derived from that area. Antibodies labeled against the protein lipocortin-1 label both microglia and neuroepithelial cells, and some of the antibodies that recognize microglial cells also label cells of neuroectodermal origin. Additionally, microglial cells can be produced in mouse neuroepithelial cell cultures thought to be devoid of mesenchymal precursors.

More recent data have shown that both microglia and astrocytes can derive from the same progenitor cell, suggesting either that some microglia are of neuroectodermal origin or that some astrocytes can be derived from mesenchymal cells, challenging the longheld view that astrocytes are of purely neuroectoder-mal origin. As such, the derivation of microglial cells has not been conclusively shown, but it is fair to say that

1. Microglial cells derive either directly from blood cells or are derived from cells of blood cell lineage.

2. During development microglial precursors invade the CNS.

3. Microglial precursor cells migrate within the CNS parenchyma to their final location.

4. Microglial cells resemble amoeboid microglia during migration but differentiate and become mature, ramified microglia once they reach their final location.

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Conquering Fear In The 21th Century

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