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Developmental Origins of Resident Central Nervous System Microglia Part 1

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Microglia are hematopoietic-derived innate immune cells that constantly survey the environment and regulate the development of the central nervous system (CNS). These cells have dynamic cellular processes that make contact with synapses and engulf cellular debris from dying neurons. The origin of microglia has been a controversial topic for decades. Recently, it was demonstrated that microglia originate in the yolk sac (YS) from YS-derived macrophages during primitive hematopoiesis and subsequently populate the embryonic brain (Ginhoux et al., 2010). However, it remains unclear whether this cohort accounts for the total resident CNS microglia population following embryonic development because of the transient spatiotemporal nature of hematopoietic sites and circulation of microglial progenitors through the developing vasculature system. Furthermore, it is also not known whether progenitors from preceding hematopoietic sites are required to seed impending hematopoietic sites for the generation of hematopoietic stem cells (HSCs). In this review, we will provide a brief context on hematopoietic development at major hematopoietic sites followed by a discussion on the current evidence regarding the origin(s) of resident CNS microglia.
Introduction
Hematopoiesis is the development of the blood system that is characterized by a spatiotemporal sequence of transient events. Each transient event is thought to follow the monophyletic theory of hematopoiesis whereby pluripotent stem cells undergo asymmetric division to either self-renew or generate lineage-restricted committed progenitor cells. These committed progenitors generate immature blood cells specific for the lymphoid, erythroid, and myeloid lineages (Chaplin et al., 2003, Laiosa et ...


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...mura, Y., Kikuta, J., Ishii, M., and Yamashita, T. (2013) Layer V cortical neurons require microglial support for survival during postnatal development. Nat. Neurosci. 16, 543-551.
Yokomizo, T., and Dzierzak, E. (2010) Three-dimensional cartography of hematopoietic clusters in the vasculature of whole mouse embryos. Development 137, 3651-3661.
Zhan, Y., Paolicelli, R.C., Sforazzini, F., Weinhard, L., Bolasco, G., Pagani, F., Vyssotski, A.L., Bifone, A., Gozzi, A., Ragozzino, D., and Gross, C.T. (2014) Deficient neuron-microglia signaling results in impaired functional brian connectivity and social behavior. Nat. Neurosci. 17, 400-406.
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Developmental Origins of Resident Central Nervous System Microglia Part 1 - Microglia are hematopoietic-derived innate immune cells that constantly survey the environment and regulate the development of the central nervous system (CNS). These cells have dynamic cellular processes that make contact with synapses and engulf cellular debris from dying neurons. The origin of microglia has been a controversial topic for decades. Recently, it was demonstrated that microglia originate in the yolk sac (YS) from YS-derived macrophages during primitive hematopoiesis and subsequently populate the embryonic brain (Ginhoux et al., 2010)....   [tags: hematopoietic-derived innate immune cells]
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