Modulation of retinoid-X-receptors differentially regulates expression of apolipoprotein genes apoc1 and apoeb by zebrafish microglia

Abstract

Transcriptome analyses performed in both human and zebrafish indicate strong expression of Apoe and Apoc1 by microglia. Apoe expression by microglia is well appreciated, but Apoc1 expression has not been well-examined. PPAR/RXR and LXR/RXR receptors appear to regulate expression of the apolipoprotein gene cluster in macrophages, but a similar role in microglia in vivo has not been studied. Here, we characterized microglial expression of apoc1 in the zebrafish central nervous system (CNS) in situ and demonstrate that in the CNS, apoc1 expression is unique to microglia. We then examined the effects of PPAR/RXR and LXR/RXR modulation on microglial expression of apoc1 and apoeb during early CNS development using a pharmacological approach. Changes in apoc1 and apoeb transcripts in response to pharmacological modulation were quantified by RT-qPCR in whole heads, and in individual microglia using hybridization chain reaction (HCR) in situ hybridization. We found that expression of apoc1 and apoeb by microglia were differentially regulated by LXR/RXR and PPAR/RXR modulating compounds, respectively, during development. Our results also suggest RXR receptors could be involved in endogenous induction of apoc1 expression by microglia. Collectively, our work supports the use of zebrafish to better understand regulation and function of these apolipoproteins in the CNS.

Keywords

• lxr-rxr
• ppar-rxr
• microglia
• apolipoproteins
• zebrafish
• cns development