Microglia and Neurodevelopment: Programming of Cognition throughout the Lifespan

Schwarz, Jaclyn M.; Bilbo, Staci D.

doi:10.1002/9781118314814.ch15

Cited by 1 publication

(1 citation statement)

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“…Zebrafish slc7a7 , xpr1b , and nlrc3‐like mutants all lack microglia (Shiau et al, ; Meireles et al, ; Rossi et al, ,b), although the embryonic retinal and brain phenotypes among these mutants remain to be determined. Non‐cell autonomous factors produced by neuroepithelial tissues, such as cell death signals and chemokines, also promote macrophage chemotaxis during development of the brain and retina (Reviewed in Polazzi and Contestabile, ; Schwarz and Bilbo, ). Two recent studies demonstrate that in zebrafish apoptotic neurons and the molecules they release mediate the entry of microglial precursors into the optic tectum and their in situ proliferation (Xu et al, ; Casano et al, ).…”

Section: Discussionmentioning

confidence: 99%

Progranulin regulates neurogenesis in the developing vertebrate retina

Walsh

Hitchcock

2017

Developmental Neurobiology

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We evaluated the expression and function of the microglia-specific growth factor, Progranulin-a (Pgrn-a) during developmental neurogenesis in the embryonic retina of zebrafish. At 24 hpf pgrn-a is expressed throughout the forebrain, but by 48 hpf pgrn-a is exclusively expressed by microglia and/or microglial precursors within the brain and retina. Knockdown of Pgrn-a does not alter the onset of neurogenic programs or increase cell death, however, in its absence, neurogenesis is significantly delayed - retinal progenitors fail to exit the cell cycle at the appropriate developmental time and postmitotic cells do not acquire markers of terminal differentiation, and microglial precursors do not colonize the retina. Given the link between Progranulin and cell cycle regulation in peripheral tissues and transformed cells, we analyzed cell cycle kinetics among retinal progenitors following Pgrn-a knockdown. Depleting Pgrn-a results in a significant lengthening of the cell cycle. These data suggest that Pgrn-a plays a dual role during nervous system development by governing the rate at which progenitors progress through the cell cycle and attracting microglial progenitors into the embryonic brain and retina. Collectively, these data show that Pgrn-a governs neurogenesis by regulating cell cycle kinetics and the transition from proliferation to cell cycle exit and differentiation.

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