Chapter 6
Retinoic Acid Signaling and Development
of the Respiratory System
Hector A. Marquez and Felicia Chen
Abstract Retinoic acid (RA), the bioactive metabolite of vitamin A (VA), has long
been recognized as a critical regulator of the development of the respiratory system.
During embryogenesis, RA signaling is involved in the development of the trachea,
airways, lung, and diaphragm. During postnatal life, RA continues to impact respiratory health. Disruption of RA activity during embryonic development produces
dramatic phenotypes in animal models and human diseases, including tracheoesophageal fistula, tracheomalacia, congenital diaphragmatic hernia (CDH), and lung
agenesis or hypoplasia. Several experimental methods have been used to target RA
pathways during the formation of the embryonic lung. These have been performed
in different animal models using gain- and loss-of-function strategies and dietary,
pharmacologic, and genetic approaches that deplete retinoid stores or disrupt retinoid
signaling. Experiments utilizing these methods have led to a deeper understanding of
RA’s role as an important signaling molecule that influences all stages of lung development. Current research is uncovering RA cross talk interactions with other embryonic signaling factors, such as fibroblast growth factors, WNT, and transforming
growth factor-beta.
Keywords Retinoic acid · Vitamin A · Retinoid · Signaling · Vitamin A
deficiency · Respiratory · Lung · Development · Embryonic · Growth ·
Vertebrates · Mammal · Avian · Retinoic acid regulated pathways
H. A. Marquez · F. Chen (B)
Pulmonary Center, Boston University School of Medicine, 72 East Concord Street, Boston,
MA R-30402118, USA
e-mail: felichen@bu.edu
H. A. Marquez
e-mail: hemarque@bu.edu
© Springer Nature Switzerland AG 2020
M. A. Asson-Batres and C. Rochette-Egly (eds.), The Biochemistry of Retinoid
Signaling III, Subcellular Biochemistry 95,
https://doi.org/10.1007/978-3-030-42282-0_6
151
Retinoic Acid Signaling and Development
of the Respiratory System
Hector A. Marquez and Felicia Chen
Abstract Retinoic acid (RA), the bioactive metabolite of vitamin A (VA), has long
been recognized as a critical regulator of the development of the respiratory system.
During embryogenesis, RA signaling is involved in the development of the trachea,
airways, lung, and diaphragm. During postnatal life, RA continues to impact respiratory health. Disruption of RA activity during embryonic development produces
dramatic phenotypes in animal models and human diseases, including tracheoesophageal fistula, tracheomalacia, congenital diaphragmatic hernia (CDH), and lung
agenesis or hypoplasia. Several experimental methods have been used to target RA
pathways during the formation of the embryonic lung. These have been performed
in different animal models using gain- and loss-of-function strategies and dietary,
pharmacologic, and genetic approaches that deplete retinoid stores or disrupt retinoid
signaling. Experiments utilizing these methods have led to a deeper understanding of
RA’s role as an important signaling molecule that influences all stages of lung development. Current research is uncovering RA cross talk interactions with other embryonic signaling factors, such as fibroblast growth factors, WNT, and transforming
growth factor-beta.
Keywords Retinoic acid · Vitamin A · Retinoid · Signaling · Vitamin A
deficiency · Respiratory · Lung · Development · Embryonic · Growth ·
Vertebrates · Mammal · Avian · Retinoic acid regulated pathways
H. A. Marquez · F. Chen (B)
Pulmonary Center, Boston University School of Medicine, 72 East Concord Street, Boston,
MA R-30402118, USA
e-mail: felichen@bu.edu
H. A. Marquez
e-mail: hemarque@bu.edu
© Springer Nature Switzerland AG 2020
M. A. Asson-Batres and C. Rochette-Egly (eds.), The Biochemistry of Retinoid
Signaling III, Subcellular Biochemistry 95,
https://doi.org/10.1007/978-3-030-42282-0_6
151