Development of ramified microglia from early macrophages in the zebrafish optic tectum

Adam J Svahn, Manuel B Graeber, Felix Ellett, Graham J Lieschke, Silke Rinkwitz, Maxwell R Bennett, Thomas S Becker

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52 Citations (Scopus)

Abstract

Microglia, the resident macrophage precursors of the brain, are necessary for the maintenance of tissue homeostasis and activated by a wide range of pathological stimuli. They have a key role in immune and inflammatory responses. Early microglia stem from primitive macrophages, however the transition from early motile forms to the ramified mature resident microglia has not been assayed in real time. In order to provide such an assay, we used zebrafish transgenic lines in which fluorescent reporter expression is driven by the promoter of macrophage expressed gene 1 (mpeg1; Ellet et al. [2011]: Blood 117(4): e49-e56,). This enabled the investigation of the development of these cells in live, intact larvae. We show that microglia develop from highly motile amoeboid cells that are engaged in phagocytosis of apoptotic cell bodies into a microglial cell type that rapidly morphs back and forth between amoeboid and ramified morphologies. These morphing microglia eventually settle into a typical mature ramified morphology. Developing microglia frequently come into contact with blood capillaries in the brain, and also frequently contact each other. Up to 10 days postfertilization, microglia were observed to undergo symmetric division. In the adult optic tectum, the microglia are highly branched, resembling mammalian microglia. In addition, the mpeg1 transgene also labeled highly branched cells in the skin overlying the optic tectum from 8-9 days postfertilization, which likely represent Langerhans cells. Thus, the development of zebrafish microglia and their cellular interactions was studied in the intact developing brain in real time and at cellular resolution. (c) 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2012.
Original languageEnglish
Pages (from-to)60 - 71
Number of pages12
JournalDevelopmental Neurobiology
Volume73
Issue number1
DOIs
Publication statusPublished - 2013

Cite this

Svahn, A. J., Graeber, M. B., Ellett, F., Lieschke, G. J., Rinkwitz, S., Bennett, M. R., & Becker, T. S. (2013). Development of ramified microglia from early macrophages in the zebrafish optic tectum. Developmental Neurobiology, 73(1), 60 - 71. https://doi.org/10.1002/dneu.22039
Svahn, Adam J ; Graeber, Manuel B ; Ellett, Felix ; Lieschke, Graham J ; Rinkwitz, Silke ; Bennett, Maxwell R ; Becker, Thomas S. / Development of ramified microglia from early macrophages in the zebrafish optic tectum. In: Developmental Neurobiology. 2013 ; Vol. 73, No. 1. pp. 60 - 71.
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Svahn, AJ, Graeber, MB, Ellett, F, Lieschke, GJ, Rinkwitz, S, Bennett, MR & Becker, TS 2013, 'Development of ramified microglia from early macrophages in the zebrafish optic tectum', Developmental Neurobiology, vol. 73, no. 1, pp. 60 - 71. https://doi.org/10.1002/dneu.22039

Development of ramified microglia from early macrophages in the zebrafish optic tectum. / Svahn, Adam J; Graeber, Manuel B; Ellett, Felix; Lieschke, Graham J; Rinkwitz, Silke; Bennett, Maxwell R; Becker, Thomas S.

In: Developmental Neurobiology, Vol. 73, No. 1, 2013, p. 60 - 71.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Development of ramified microglia from early macrophages in the zebrafish optic tectum

AU - Svahn, Adam J

AU - Graeber, Manuel B

AU - Ellett, Felix

AU - Lieschke, Graham J

AU - Rinkwitz, Silke

AU - Bennett, Maxwell R

AU - Becker, Thomas S

PY - 2013

Y1 - 2013

N2 - Microglia, the resident macrophage precursors of the brain, are necessary for the maintenance of tissue homeostasis and activated by a wide range of pathological stimuli. They have a key role in immune and inflammatory responses. Early microglia stem from primitive macrophages, however the transition from early motile forms to the ramified mature resident microglia has not been assayed in real time. In order to provide such an assay, we used zebrafish transgenic lines in which fluorescent reporter expression is driven by the promoter of macrophage expressed gene 1 (mpeg1; Ellet et al. [2011]: Blood 117(4): e49-e56,). This enabled the investigation of the development of these cells in live, intact larvae. We show that microglia develop from highly motile amoeboid cells that are engaged in phagocytosis of apoptotic cell bodies into a microglial cell type that rapidly morphs back and forth between amoeboid and ramified morphologies. These morphing microglia eventually settle into a typical mature ramified morphology. Developing microglia frequently come into contact with blood capillaries in the brain, and also frequently contact each other. Up to 10 days postfertilization, microglia were observed to undergo symmetric division. In the adult optic tectum, the microglia are highly branched, resembling mammalian microglia. In addition, the mpeg1 transgene also labeled highly branched cells in the skin overlying the optic tectum from 8-9 days postfertilization, which likely represent Langerhans cells. Thus, the development of zebrafish microglia and their cellular interactions was studied in the intact developing brain in real time and at cellular resolution. (c) 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2012.

AB - Microglia, the resident macrophage precursors of the brain, are necessary for the maintenance of tissue homeostasis and activated by a wide range of pathological stimuli. They have a key role in immune and inflammatory responses. Early microglia stem from primitive macrophages, however the transition from early motile forms to the ramified mature resident microglia has not been assayed in real time. In order to provide such an assay, we used zebrafish transgenic lines in which fluorescent reporter expression is driven by the promoter of macrophage expressed gene 1 (mpeg1; Ellet et al. [2011]: Blood 117(4): e49-e56,). This enabled the investigation of the development of these cells in live, intact larvae. We show that microglia develop from highly motile amoeboid cells that are engaged in phagocytosis of apoptotic cell bodies into a microglial cell type that rapidly morphs back and forth between amoeboid and ramified morphologies. These morphing microglia eventually settle into a typical mature ramified morphology. Developing microglia frequently come into contact with blood capillaries in the brain, and also frequently contact each other. Up to 10 days postfertilization, microglia were observed to undergo symmetric division. In the adult optic tectum, the microglia are highly branched, resembling mammalian microglia. In addition, the mpeg1 transgene also labeled highly branched cells in the skin overlying the optic tectum from 8-9 days postfertilization, which likely represent Langerhans cells. Thus, the development of zebrafish microglia and their cellular interactions was studied in the intact developing brain in real time and at cellular resolution. (c) 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2012.

UR - http://www.ncbi.nlm.nih.gov/pubmed/22648905

U2 - 10.1002/dneu.22039

DO - 10.1002/dneu.22039

M3 - Article

VL - 73

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EP - 71

JO - Developmental Neurobiology

JF - Developmental Neurobiology

SN - 1932-8451

IS - 1

ER -