5 Retinoic Acid Signaling and Heart Development
139
(ChIP-seq) (Barski and Zhao 2009; Delacroix et al. 2010; Moutier et al. 2012). In the
future, newer tools that require fewer cells, including single-cell RNA-seq (scRNAseq) (Wagner et al. 2016; Tanay and Regev 2017), Assay for Transposase-Accessible
Chromatin (ATAC-seq) (Buenrostro et al. 2013; Dirks et al. 2016), Cleavage under
targets and release using nuclease (CUT&RUN) (Skene et al. 2018), and Cleavage
Under Targets and Tagmentation (CUT&Tag) (Kaya-Okur et al. 2019), will provide
more powerful approaches to integrate and interrogate RA signaling in normal and
aberrant heart development.
Future work is needed to deconvolute RA-dependent epigenetic and transcriptional mechanisms. Specifically, the identity of all of the effectors that act in concert
with RA remains unknown, the nature of interactions, direct or otherwise, between
molecular participants is uncharted, and the identification of gene regulatory networks that govern how different levels of RA often lead to improper feedback and
the same overt phenotypes remains a mystery. Ultimately, given RA signaling’s role
as a central integrator of many other signaling pathways, the prospect that future
endeavors might reveal the etiologies of CHDs makes us optimistic that a clearer
understanding of cardiac development and the generation of novel therapeutics may
soon be on the horizon.
References
Abdul-Wajid S, Demarest BL, Yost HJ (2018) Loss of embryonic neural crest derived cardiomyocytes causes adult onset hypertrophic cardiomyopathy in zebrafish. Nat Commun. 9:1–11.
https://doi.org/10.1038/s41467-018-07054-8
Abu-Abed S, Dollé P, Metzger D, Beckett B, Chambon P, Petkovich M (2001) The retinoic acidmetabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity,
and development of posterior structures. Genes Dev 15:226–40
Abu-Issa R, Kirby ML (2008) Patterning of the heart field in the chick. Dev Biol 319:223–233.
https://doi.org/10.1016/j.ydbio.2008.04.014
Adams MK, Belyaeva OV, Wu L, Kedishvili NY (2014) The retinaldehyde reductase activity of
DHRS3 is reciprocally activated by retinol dehydrogenase 10 to control retinoid homeostasis. J
Biol Chem 289:14868–80. https://doi.org/10.1074/jbc.M114.552257
Amengual J, Zhang N, Kemerer M, Maeda T, Palczewski K, Von Lintig J (2014) STRA6 is critical
for cellular vitamin A uptake and homeostasis. Hum Mol Genet 23:5402–5417. https://doi.org/
10.1093/hmg/ddu258
Bakkers J (2011) Zebrafish as a model to study cardiac development and human cardiac disease.
Cardiovasc Res 91:279–288. https://doi.org/10.1093/cvr/cvr098
Barski A, Zhao K (2009) Genomic location analysis by ChIP-Seq. J Cell Biochem 107:11–8. https://
doi.org/10.1002/jcb.22077
Batten ML, Imanishi Y, Maeda T, Tu DC, Moise AR, Bronson D, Possin D, Van Gelder RN, Baehr
W, Palczewski K (2004) Lecithin-retinol Acyltransferase Is Essential for Accumulation of Alltrans -Retinyl Esters in the Eye and in the Liver. J Biol Chem 279:10422–10432. https://doi.org/
10.1074/jbc.M312410200
Berry DC, Jacobs H, Marwarha G, Gely-Pernot A, O’Byrne SM, DeSantis D, Klopfenstein M, Feret
B, Dennefeld C, Blaner WS, Croniger CM, Mark M, Noy N, Ghyselinck NB (2013) The STRA6
receptor is essential for retinol-binding protein-induced insulin resistance but not for maintaining
139
(ChIP-seq) (Barski and Zhao 2009; Delacroix et al. 2010; Moutier et al. 2012). In the
future, newer tools that require fewer cells, including single-cell RNA-seq (scRNAseq) (Wagner et al. 2016; Tanay and Regev 2017), Assay for Transposase-Accessible
Chromatin (ATAC-seq) (Buenrostro et al. 2013; Dirks et al. 2016), Cleavage under
targets and release using nuclease (CUT&RUN) (Skene et al. 2018), and Cleavage
Under Targets and Tagmentation (CUT&Tag) (Kaya-Okur et al. 2019), will provide
more powerful approaches to integrate and interrogate RA signaling in normal and
aberrant heart development.
Future work is needed to deconvolute RA-dependent epigenetic and transcriptional mechanisms. Specifically, the identity of all of the effectors that act in concert
with RA remains unknown, the nature of interactions, direct or otherwise, between
molecular participants is uncharted, and the identification of gene regulatory networks that govern how different levels of RA often lead to improper feedback and
the same overt phenotypes remains a mystery. Ultimately, given RA signaling’s role
as a central integrator of many other signaling pathways, the prospect that future
endeavors might reveal the etiologies of CHDs makes us optimistic that a clearer
understanding of cardiac development and the generation of novel therapeutics may
soon be on the horizon.
References
Abdul-Wajid S, Demarest BL, Yost HJ (2018) Loss of embryonic neural crest derived cardiomyocytes causes adult onset hypertrophic cardiomyopathy in zebrafish. Nat Commun. 9:1–11.
https://doi.org/10.1038/s41467-018-07054-8
Abu-Abed S, Dollé P, Metzger D, Beckett B, Chambon P, Petkovich M (2001) The retinoic acidmetabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity,
and development of posterior structures. Genes Dev 15:226–40
Abu-Issa R, Kirby ML (2008) Patterning of the heart field in the chick. Dev Biol 319:223–233.
https://doi.org/10.1016/j.ydbio.2008.04.014
Adams MK, Belyaeva OV, Wu L, Kedishvili NY (2014) The retinaldehyde reductase activity of
DHRS3 is reciprocally activated by retinol dehydrogenase 10 to control retinoid homeostasis. J
Biol Chem 289:14868–80. https://doi.org/10.1074/jbc.M114.552257
Amengual J, Zhang N, Kemerer M, Maeda T, Palczewski K, Von Lintig J (2014) STRA6 is critical
for cellular vitamin A uptake and homeostasis. Hum Mol Genet 23:5402–5417. https://doi.org/
10.1093/hmg/ddu258
Bakkers J (2011) Zebrafish as a model to study cardiac development and human cardiac disease.
Cardiovasc Res 91:279–288. https://doi.org/10.1093/cvr/cvr098
Barski A, Zhao K (2009) Genomic location analysis by ChIP-Seq. J Cell Biochem 107:11–8. https://
doi.org/10.1002/jcb.22077
Batten ML, Imanishi Y, Maeda T, Tu DC, Moise AR, Bronson D, Possin D, Van Gelder RN, Baehr
W, Palczewski K (2004) Lecithin-retinol Acyltransferase Is Essential for Accumulation of Alltrans -Retinyl Esters in the Eye and in the Liver. J Biol Chem 279:10422–10432. https://doi.org/
10.1074/jbc.M312410200
Berry DC, Jacobs H, Marwarha G, Gely-Pernot A, O’Byrne SM, DeSantis D, Klopfenstein M, Feret
B, Dennefeld C, Blaner WS, Croniger CM, Mark M, Noy N, Ghyselinck NB (2013) The STRA6
receptor is essential for retinol-binding protein-induced insulin resistance but not for maintaining