BMP and RA signaling cooperate to regulate Apolipoprotein C1 expression during embryonic development

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

“…Various in vitro studies have examined the role of LXR-RXR and PPAR-RXR receptors in the regulation of the apolipoprotein gene cluster in macrophages and other cell types in vitro ( Chawla et al, 2001 ; Dahabreh and Medh, 2012 ; Mak et al, 2002 ; Subramanian et al, 2017 ). Further, there are reports of RA regulation of these genes in astrocytes ( Zhao et al, 2014 ), indirect effects of RA on apoc1 in the zebrafish embryo ( Wang et al, 2015 ), as well as LXR regulation in both astrocytes and macrophages ( Laffitte et al, 2001b ; Liang et al, 2004 ; Mak et al, 2002 ). Using in silico analysis of the ∼5 kb upstream region of zebrafish apoc1 , we found predicted binding sites for RAR and RXR receptors, as well as a predicted PPAR-RXR site ( …”

“…We considered that RXR heterodimers could be important in this regard, and that modulation of these receptors could affect Apoc1 expression by microglia in vivo , given that published in vitro studies have examined the role of LXR-RXR and PPAR-RXR receptors in the regulation of the apolipoprotein gene cluster in macrophages ( Chawla et al, 2001 ; Dahabreh and Medh, 2012 ; Mak et al, 2002 ; Subramanian et al, 2017 ). Also notable, there are reports of retinoic acid (RA) regulation of apolipoprotein genes in astrocytes ( Zhao et al, 2014 ), indirect effects of RA on apoc1 in the zebrafish embryo ( Wang et al, 2015 ), as well as LXR regulation in both astrocytes and macrophages ( Laffitte et al, 2001b ; Liang et al, 2004 ; Mak et al, 2002 ). Considering these reports and the advantages of the zebrafish model for pharmacological manipulations via immersion and in situ imaging, as well as transcriptome analyses indicating conserved expression of Apoc1 by microglia in both human and zebrafish as discussed above, the zebrafish could provide an excellent model organism to probe this gene.…”

The channel catfish genome sequence provides insights into the evolution of scale formation in teleosts

“…The most prominent of the upregulated genes were apolipoprotein and SCPP genes. Apolipoproteins are known to promote fat efflux 41 and have been reported to be involved in scale development in zebrafish 42 43 , suggesting their role in development of mineralized tissues. SCPP genes arose from SPARCL1 through gene duplication 44 45 , and are involved in skeletal and dental tissue mineralization 46 47 48 49 50 51 .…”

Optogenetic investigation of BMP target gene expression diversity

“…We identified 16 high-confidence target genes that are significantly upregulated in bmp -overexpressing embryos and downregulated in embryos overexpressing the BMP inhibitor chordin ( Figure 1—figure supplement 1A–D and Supplementary file 1 ). 14 of these genes ( apoc1l , bambia , bmp4 , cdx4 , eve1 , foxi1 , gata2a , id2a , klf2b , smad6a , smad7 , sizzled , tfap2c , and ved ) are known to be positively regulated by BMP in zebrafish ( Kashiwada et al, 2015 ; Wang et al, 2015 ; Kotkamp et al, 2014 ; Wang et al, 2013 ; Das and Crump, 2012 ; de Pater et al, 2012 ; Kwon et al, 2010 ; Li and Cornell, 2007 ; Poulain et al, 2006 ; Chong et al, 2005 ; Davidson et al, 2003 ; Martyn and Schulte-Merker, 2003 ; Nissen et al, 2003 ; Solomon et al, 2003 ; Yabe et al, 2003 ; Pogoda and Meyer, 2002 ; Shimizu et al, 2002 ; Oates et al, 2001 ; Tsang et al, 2000 ; Chin et al, 1997 ; Nikaido et al, 1997 ; Hammerschmidt et al, 1996a ; Hammerschmidt et al, 1996b ; Mullins et al, 1996 ; Detrich et al, 1995 ; Joly et al, 1993 ; Joly et al, 1992 ), whereas crabp2b ( Sharma et al, 2005 ) and znfl2b ( Hogan et al, 2006 ) have not previously been implicated as BMP targets. Four of the 16 target genes encode repressors of BMP signaling ( bambia , sizzled , smad6a , and smad7 ) and one encodes bmp4 , consistent with roles for negative and positive feedbacks in TGF-β-mediated patterning ( Zinski et al, 2018 ).…”