Retinoic Acid Signaling and Development of the Respiratory System

  • Hector A. Marquez
  • Felicia ChenEmail author
Part of the Subcellular Biochemistry book series (SCBI, volume 95)


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.


Retinoic acid Vitamin A Retinoid Signaling Vitamin A deficiency Respiratory Lung Development Embryonic Growth Vertebrates Mammal Avian Retinoic acid regulated pathways 



Alpha-actin-2 or alpha smooth muscle actin


Aldehyde dehydrogenase


Airway smooth muscle


Bone morphogenetic protein 4


A pan-retinoic acid receptor inverse agonist


Congenital diaphragmatic hernia


Chronic obstructive pulmonary disease




Dickkopf WNT signaling pathway inhibitor 1


Embryonic day


Fibroblast growth factor


GLI-Kruppel family member




Myosin heavy chain 11




Not determined


NK2 homeobox 1


Post coitum


Pulmonary hypertension


Postnatal day


Retinoic acid


Retinoic acid deficiency or retinoic acid-deficient


Retinaldehyde dehydrogenase


Retinoic acid receptor


Retinoic acid response element


Sonic hedgehog


Serum response factor


Stimulated by retinoic acid 6




Tracheoesophageal fistula


Transforming growth factor-beta


Vitamin A


Vitamin A deficiency or vitamin A-deficient


Wingless-type MMTV integration site family


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Pulmonary CenterBoston University School of MedicineBostonUSA

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