Retinoic Acid Signaling and Heart Development

Zaffran, Stéphane; Niederreither, Karen

doi:10.1002/9781118628003.ch15

Cited by 6 publications

(9 citation statements)

References 95 publications

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“…A significant body of research has now firmly established that RA acts during early embryonic development in a dose-specific fashion. These roles of RA in development of the body are highly conserved across vertebrates, and these findings are summarized in several excellent publications (Cunningham & Duester, 2015;Duester, 2008;Glover, Renaud, & Rijli, 2006;Lewandoski & Mackem, 2009;Luo, Sakai, Wagner, & Dräger, 2006;Maden, 2007;Rhinn & Doll e, 2012;Weston, Hoffman, & Underhill, 2003;Zaffran & Niederreither, 2015).…”

Section: R a Bi Oge N Esi S A N D Si Gn Al I Ng P A Th Wa Ymentioning

confidence: 98%

Generating retinoic acid gradients by local degradation during craniofacial development: One cell's cue is another cell's poison

Dubey

Rose

Jones

et al. 2018

Genesis

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Retinoic acid (RA) is a vital morphogen for early patterning and organogenesis in the developing embryo. RA is a diffusible, lipophilic molecule that signals via nuclear RA receptor heterodimeric units that regulate gene expression by interacting with RA response elements in promoters of a significant number of genes. For precise RA signaling, a robust gradient of the morphogen is required. The developing embryo contains regions that produce RA, and specific intracellular concentrations of RA are created through local degradation mediated by Cyp26 enzymes. In order to elucidate the mechanisms by which RA executes precise developmental programs, the kinetics of RA metabolism must be clearly understood. Recent advances in techniques for endogenous RA detection and quantification have paved the way for mechanistic studies to shed light on downstream gene expression regulation coordinated by RA. It is increasingly coming to light that RA signaling operates not only at precise concentrations but also employs mechanisms of degradation and feedback inhibition to self-regulate its levels. A global gradient of RA throughout the embryo is often found concurrently with several local gradients, created by juxtaposed domains of RA synthesis and degradation. The existence of such local gradients has been found especially critical for the proper development of craniofacial structures that arise from the neural crest and the cranial placode populations. In this review, we summarize the current understanding of how local gradients of RA are established in the embryo and their impact on craniofacial development.

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Section: R a Bi Oge N Esi S A N D Si Gn Al I Ng P A Th Wa Ymentioning

confidence: 98%

Generating retinoic acid gradients by local degradation during craniofacial development: One cell's cue is another cell's poison

Dubey

Rose

Jones

et al. 2018

Genesis

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“…Retinoic acid (RA) is the bioactive derivative of vitamin A and has proved to be an important signaling molecule for heart development in vertebrates (Niederreither and Dollé, ; Zaffran et al, ; Zaffran and Niederreither, ). Both excessive and reduced RA signaling lead to cardiovascular malformations, in particular outflow tract (OFT) defects in the form of transposition of the great arteries, double‐outlet right ventricle, persistent truncus arteriosus (PTA) and ventricular septal defects, as well as aortic arch anomalies (Pan and Baker, ).…”

Section: Introductionmentioning

confidence: 99%

Cardiac outflow morphogenesis depends on effects of retinoic acid signaling on multiple cell lineages

Robrini

Etchevers

Ryckebüsch

et al. 2015

Developmental Dynamics

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Background: Retinoic acid (RA), the bioactive derivative of vitamin A, is essential for vertebrate heart development. Both excess and reduced RA signaling lead to cardiovascular malformations affecting the outflow tract (OFT). To address the cellular mechanisms underlying the effects of RA signaling during OFT morphogenesis, we used transient maternal RA supplementation to rescue the early lethality resulting from inactivation of the murine retinaldehyde dehydrogenase 2 (Raldh2) gene. Results: By embryonic day 13.5, all rescued Raldh2 2/2 hearts exhibit severe, reproducible OFT septation defects, although wild-type and Raldh2 1/2 littermates have normal hearts. Cardiac neural crest cells (cNCC) were present in OFT cushions of Raldh2 2/2 mutant embryos but ectopically located in the periphery of the endocardial cushions, rather than immediately underlying the endocardium. Excess mesenchyme was generated by Raldh2 2/2 mutant endocardium, which displaced cNCC derivatives from their subendocardial, medial position. Conclusions: RA signaling affects not only cNCC numbers but also their position relative to endocardial mesenchyme during the septation process. Our study shows that inappropriate coordination between the different cell types of the OFT perturbs its morphogenesis and leads to a severe congenital heart defect, persistent truncus arteriosus. Developmental Dynamics 245:388-401, 2016. V C 2015 Wiley Periodicals, Inc.

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“…Cardiac defects largely affect the formation/remodelling of the pharyngeal arch arteries into the great vessels and the development of the outflow and inflow tracts by addition of secondary heart field progenitors at the arterial and venous poles of the heart. Neural-crest driven septation of the outflow tract is also abnormal leading to CAT and aorticopulmonary windows [9,[76][77][78][79][80]101,[105][106][107][108][109], reviewed [10][11][12][13][14]110].…”

Section: Embryonic Defects Arising From Dysregulated Ra Signallingmentioning

confidence: 99%

“…Normal development of the pharyngeal system and the neural crest are important for cardiovascular development (reviewed by [340][341][342][343]). Retinoic acid signalling is necessary for this development to take place [12][13][14]. All three Cyp26 genes are expressed in differing pharyngeal tissues during mouse development.…”

Section: Pharyngeal and Cardiovascular Systemsmentioning

confidence: 99%

“…Whilst substantial progress has been made regarding the function of RALDHs during development, much less is known about the CYP26s. This review gives a brief overview of the RA pathway and function in development, already well-described in numerous reviews, for example [10][11][12][13][14][15][16] and then focusses upon the role of the RA-degrading CYP26 enzymes during embryonic development and in regenerative processes.…”

Section: Introductionmentioning

confidence: 99%

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Regulating Retinoic Acid Availability during Development and Regeneration: The Role of the CYP26 Enzymes

Roberts

2020

JDB

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This review focuses on the role of the Cytochrome p450 subfamily 26 (CYP26) retinoic acid (RA) degrading enzymes during development and regeneration. Cyp26 enzymes, along with retinoic acid synthesising enzymes, are absolutely required for RA homeostasis in these processes by regulating availability of RA for receptor binding and signalling. Cyp26 enzymes are necessary to generate RA gradients and to protect specific tissues from RA signalling. Disruption of RA homeostasis leads to a wide variety of embryonic defects affecting many tissues. Here, the function of CYP26 enzymes is discussed in the context of the RA signalling pathway, enzymatic structure and biochemistry, human genetic disease, and function in development and regeneration as elucidated from animal model studies.

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Retinoic Acid Signaling and Heart Development

Cited by 6 publications

References 95 publications

Generating retinoic acid gradients by local degradation during craniofacial development: One cell's cue is another cell's poison

Generating retinoic acid gradients by local degradation during craniofacial development: One cell's cue is another cell's poison

Cardiac outflow morphogenesis depends on effects of retinoic acid signaling on multiple cell lineages

Regulating Retinoic Acid Availability during Development and Regeneration: The Role of the CYP26 Enzymes

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