Retinoids in Embryonic Development

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (15 October 2019) | Viewed by 64573

Special Issue Editors


E-Mail Website
Guest Editor
Laboratoire de Biologie du Développement de Villefranche-sur-Mer (CNRS/Sorbonne Université), Institut de la Mer de Villefranche-sur-Mer, 06230 Villefranche-sur-Mer, France
Interests: evolution of development; neural development; nuclear hormone receptors; endocrine disruption; alternative model organisms; amphioxus; lampreys; sea urchins; mussels
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, USA
Interests: retinoic acid; metabolism; tooth, evo–devo; model organism; zebrafish

Special Issue Information

Dear Colleagues,

Animal development is characterized by the deployment of highly conserved sets of morphogens and transcription factors that contribute to the patterning and formation of a startling variety of adult morphologies. One of these conserved effector–receptor systems is retinoic acid (RA) signaling that plays critical roles not only during development, but also in the regulation of adult homeostasis. Within a target cell, RA signaling is activated by the binding of all-trans RA, the biologically active metabolite of vitamin A, to heterodimers of two nuclear receptors, the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). Since the discovery of these nuclear RA receptors a little bit over 30 years ago, an enormous effort has been undertaken by the scientific community to disclose both the molecular intricacies of the RA signal and the biological readouts of its activity. It is probably safe to say that the scientific community has already come a long way to fulfill this ambitious aim, but as groundbreaking discoveries are being made, new research questions emerge. This Special Issue intends to provide examples of current exciting work on RA signaling, with a special focus on developmental processes in the embryo, highlighting intriguing results and exciting perspectives for the future of RA research.

Dr. Michael Schubert
Dr. Yann Gibert
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Animal models
  • Developmental mechanisms 
  • Epigenetic regulation 
  • Genomic and non-genomic processes
  • Origin and evolution of retinoic acid functions 
  • Receptor-ligand interactions 
  • Retinoid metabolism 
  • Retinoid pharmacology 
  • Retinoid receptors 
  • Vitamin A-dependent signaling

Published Papers (13 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

4 pages, 180 KiB  
Editorial
Retinoids in Embryonic Development
by Michael Schubert and Yann Gibert
Biomolecules 2020, 10(9), 1278; https://doi.org/10.3390/biom10091278 - 04 Sep 2020
Cited by 11 | Viewed by 2138
Abstract
Retinoids constitute a class of compounds chemically related to vitamin A [...] Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)

Research

Jump to: Editorial, Review

16 pages, 3320 KiB  
Article
Of Retinoids and Organotins: The Evolution of the Retinoid X Receptor in Metazoa
by Elza Fonseca, Raquel Ruivo, Débora Borges, João N. Franco, Miguel M. Santos and L. Filipe C. Castro
Biomolecules 2020, 10(4), 594; https://doi.org/10.3390/biom10040594 - 11 Apr 2020
Cited by 17 | Viewed by 2618
Abstract
Nuclear receptors (NRs) are transcription factors accomplishing a multiplicity of functions, essential for organismal homeostasis. Among their numerous members, the retinoid X receptor (RXR) is a central player of the endocrine system, with a singular ability to operate as a homodimer or a [...] Read more.
Nuclear receptors (NRs) are transcription factors accomplishing a multiplicity of functions, essential for organismal homeostasis. Among their numerous members, the retinoid X receptor (RXR) is a central player of the endocrine system, with a singular ability to operate as a homodimer or a heterodimer with other NRs. Additionally, RXR has been found to be a critical actor in various processes of endocrine disruption resulting from the exposure to a known class of xenobiotics termed organotins (e.g., tributyltin (TBT)), including imposex in gastropod molluscs and lipid perturbation across different metazoan lineages. Thus, given its prominent physiological and endocrine role, RXR is present in the genomes of most extant metazoan species examined to date. Here, we expand on the phylogenetic distribution of RXR across the metazoan tree of life by exploring multiple next-generation sequencing projects of protostome lineages. By addressing amino acid residue conservation in combination with cell-based functional assays, we show that RXR induction by 9-cis retinoic acid (9cisRA) and TBT is conserved in more phyla than previously described. Yet, our results highlight distinct activation efficacies and alternative modes of RXR exploitation by the organotin TBT, emphasizing the need for broader species sampling to clarify the mechanistic activation of RXR. Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)
Show Figures

Figure 1

13 pages, 2505 KiB  
Article
Retinoic Acid Signaling Regulates the Metamorphosis of Feather Stars (Crinoidea, Echinodermata): Insight into the Evolution of the Animal Life Cycle
by Shumpei Yamakawa, Yoshiaki Morino, Hisanori Kohtsuka and Hiroshi Wada
Biomolecules 2020, 10(1), 37; https://doi.org/10.3390/biom10010037 - 25 Dec 2019
Cited by 7 | Viewed by 4107
Abstract
Many marine invertebrates have a life cycle with planktonic larvae, although the evolution of this type of life cycle remains enigmatic. We recently proposed that the regulatory mechanism of life cycle transition is conserved between jellyfish (Cnidaria) and starfish (Echinoderm); retinoic acid (RA) [...] Read more.
Many marine invertebrates have a life cycle with planktonic larvae, although the evolution of this type of life cycle remains enigmatic. We recently proposed that the regulatory mechanism of life cycle transition is conserved between jellyfish (Cnidaria) and starfish (Echinoderm); retinoic acid (RA) signaling regulates strobilation and metamorphosis, respectively. However, the function of RA signaling in other animal groups is poorly understood in this context. Here, to determine the ancestral function of RA signaling in echinoderms, we investigated the role of RA signaling during the metamorphosis of the feather star, Antedon serrata (Crinoidea, Echinodermata). Although feather stars have different larval forms from starfish, we found that exogenous RA treatment on doliolaria larvae induced metamorphosis, like in starfish. Furthermore, blocking RA synthesis or binding to the RA receptor suppressed metamorphosis. These results suggested that RA signaling functions as a regulator of metamorphosis in the ancestor of echinoderms. Our data provides insight into the evolution of the animal life cycle from the viewpoint of RA signaling. Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)
Show Figures

Figure 1

24 pages, 5920 KiB  
Article
Retinoic Acid Signaling Is Associated with Cell Proliferation, Muscle Cell Dedifferentiation, and Overall Rudiment Size during Intestinal Regeneration in the Sea Cucumber, Holothuria glaberrima
by Jorge Viera-Vera and José E. García-Arrarás
Biomolecules 2019, 9(12), 873; https://doi.org/10.3390/biom9120873 - 13 Dec 2019
Cited by 9 | Viewed by 3104
Abstract
Almost every organism has the ability of repairing damaged tissues or replacing lost and worn out body parts, nevertheless the degree of the response substantially differs between each species. Adult sea cucumbers from the Holothuria glaberrima species can eviscerate various organs and the [...] Read more.
Almost every organism has the ability of repairing damaged tissues or replacing lost and worn out body parts, nevertheless the degree of the response substantially differs between each species. Adult sea cucumbers from the Holothuria glaberrima species can eviscerate various organs and the intestinal system is the first one to regenerate. This process involves the formation of a blastema-like structure that derives from the torn mesentery edges by the intervention of specific cellular processes (e.g., cell dedifferentiation and division). Still, the genetic networks controlling the regenerative response in this model system are just starting to be unraveled. In this work we examined if and how the retinoic acid (RA) signaling pathway is involved in the regenerative response of this deuterostome. We first identified and characterized the holothurian orthologs for short chain dehydrogenase/reductase 7 (SDR7) and aldehyde dehydrogenase family 8A1 (ALDH8A1), two enzymes respectively associated with retinaldehyde and RA anabolism. We then showed that the SDR7 transcript was differentially expressed during specific stages of intestinal regeneration while ALDH8A1 did not show significant differences in regenerating tissues when compared to those of normal (non-eviscerated) organisms. Finally, we investigated the consequences of modulating RA signaling during intestinal regeneration using pharmacological tools. We showed that application of an inhibitor (citral) of the enzyme synthesizing RA or a retinoic acid receptor (RAR) antagonist (LE135) resulted in organisms with a significantly smaller intestinal rudiment when compared to those treated with DMSO (vehicle). The two inhibitors caused a reduction in cell division and cell dedifferentiation in the new regenerate when compared to organisms treated with DMSO. Results of treatment with tazarotene (an RAR agonist) were not significantly different from the control. Taken together, these results suggest that the RA signaling pathway is regulating the cellular processes that are crucial for intestinal regeneration to occur. Thus, RA might be playing a role in echinoderm regeneration that is similar to what has been described in other animal systems. Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)
Show Figures

Figure 1

20 pages, 2098 KiB  
Article
Retinol Saturase Knock-Out Mice are Characterized by Impaired Clearance of Apoptotic Cells and Develop Mild Autoimmunity
by Zsolt Sarang, Tibor Sághy, Zsófia Budai, László Ujlaky-Nagy, Judit Bedekovics, Lívia Beke, Gábor Méhes, Gábor Nagy, Ralph Rühl, Alexander R. Moise, Krzysztof Palczewski and Zsuzsa Szondy
Biomolecules 2019, 9(11), 737; https://doi.org/10.3390/biom9110737 - 13 Nov 2019
Cited by 10 | Viewed by 3540
Abstract
Apoptosis and the proper clearance of apoptotic cells play a central role in maintaining tissue homeostasis. Previous work in our laboratory has shown that when a high number of cells enters apoptosis in a tissue, the macrophages that engulf them produce retinoids to [...] Read more.
Apoptosis and the proper clearance of apoptotic cells play a central role in maintaining tissue homeostasis. Previous work in our laboratory has shown that when a high number of cells enters apoptosis in a tissue, the macrophages that engulf them produce retinoids to enhance their own phagocytic capacity by upregulating several phagocytic genes. Our data indicated that these retinoids might be dihydroretinoids, which are products of the retinol saturase (RetSat) pathway. In the present study, the efferocytosis of RetSat-null mice was investigated. We show that among the retinoid-sensitive phagocytic genes, only transglutaminase 2 responded in macrophages and in differentiating monocytes to dihydroretinol. Administration of dihydroretinol did not affect the expression of the tested genes differently between differentiating wild type and RetSat-null monocytes, despite the fact that the expression of RetSat was induced. However, in the absence of RetSat, the expression of numerous differentiation-related genes was altered. Among these, impaired production of MFG-E8, a protein that bridges apoptotic cells to the αvβ35 integrin receptors of macrophages, resulted in impaired efferocytosis, very likely causing the development of mild autoimmunity in aged female mice. Our data indicate that RetSat affects monocyte/macrophage differentiation independently of its capability to produce dihydroretinol at this stage. Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)
Show Figures

Figure 1

15 pages, 2218 KiB  
Article
Divergent Roles of CYP26B1 and Endogenous Retinoic Acid in Mouse Fetal Gonads
by Laura Bellutti, Emilie Abby, Sophie Tourpin, Sébastien Messiaen, Delphine Moison, Emilie Trautmann, Marie-Justine Guerquin, Virginie Rouiller-Fabre, René Habert and Gabriel Livera
Biomolecules 2019, 9(10), 536; https://doi.org/10.3390/biom9100536 - 26 Sep 2019
Cited by 13 | Viewed by 3384
Abstract
In female mammals, germ cells enter meiosis in the fetal ovaries, while in males, meiosis is prevented until postnatal development. Retinoic acid (RA) is considered the main inducer of meiotic entry, as it stimulates Stra8 which is required for the mitotic/meiotic switch. In [...] Read more.
In female mammals, germ cells enter meiosis in the fetal ovaries, while in males, meiosis is prevented until postnatal development. Retinoic acid (RA) is considered the main inducer of meiotic entry, as it stimulates Stra8 which is required for the mitotic/meiotic switch. In fetal testes, the RA-degrading enzyme CYP26B1 prevents meiosis initiation. However, the role of endogenous RA in female meiosis entry has never been demonstrated in vivo. In this study, we demonstrate that some effects of RA in mouse fetal gonads are not recapitulated by the invalidation or up-regulation of CYP26B1. In organ culture of fetal testes, RA stimulates testosterone production and inhibits Sertoli cell proliferation. In the ovaries, short-term inhibition of RA-signaling does not decrease Stra8 expression. We develop a gain-of-function model to express CYP26A1 or CYP26B1. Only CYP26B1 fully prevents STRA8 induction in female germ cells, confirming its role as part of the meiotic prevention machinery. CYP26A1, a very potent RA degrading enzyme, does not impair the formation of STRA8-positive cells, but decreases Stra8 transcription. Collectively, our data reveal that CYP26B1 has other activities apart from metabolizing RA in fetal gonads and suggest a role of endogenous RA in amplifying Stra8, rather than being the initial inducer of Stra8. These findings should reactivate the quest to identify meiotic preventing or inducing substances. Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)
Show Figures

Figure 1

17 pages, 2400 KiB  
Article
Inhibition of Rho GTPases in Invertebrate Growth Cones Induces a Switch in Responsiveness to Retinoic Acid
by Alysha Johnson, Tamara I. N. Nasser and Gaynor E. Spencer
Biomolecules 2019, 9(9), 460; https://doi.org/10.3390/biom9090460 - 07 Sep 2019
Cited by 4 | Viewed by 2482
Abstract
During development, growth cones are essential for axon pathfinding by sensing numerous guidance cues in their environment. Retinoic acid, the metabolite of vitamin A, is important for neurite outgrowth during vertebrate development, but may also play a role in axon guidance, though little [...] Read more.
During development, growth cones are essential for axon pathfinding by sensing numerous guidance cues in their environment. Retinoic acid, the metabolite of vitamin A, is important for neurite outgrowth during vertebrate development, but may also play a role in axon guidance, though little is known of the cellular mechanisms involved. Our previous studies showed that retinoid-induced growth cone turning of invertebrate motorneurons requires local protein synthesis and calcium influx. However, the signalling pathways that link calcium influx to cytoskeletal dynamics involved in retinoid-mediated growth cone turning are not currently known. The Rho GTPases, Cdc42 and Rac, are known regulators of the growth cone cytoskeleton. Here, we demonstrated that inhibition of Cdc42 or Rac not only prevented growth cone turning toward retinoic acid but could also induce a switch in growth cone responsiveness to chemorepulsion or growth cone collapse. However, the effects of Cdc42 or Rac inhibition on growth cone responsiveness differed, depending on whether the turning was induced by the all-trans or 9-cis retinoid isomer. The effects also differed depending on whether the growth cones maintained communication with the cell body. These data strongly suggest that Cdc42 and Rac are downstream effectors of retinoic acid during growth cone guidance. Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)
Show Figures

Figure 1

Review

Jump to: Editorial, Research

8 pages, 489 KiB  
Review
The Role of Retinoic Acid in Establishing the Early Limb Bud
by Eleanor Feneck and Malcolm Logan
Biomolecules 2020, 10(2), 312; https://doi.org/10.3390/biom10020312 - 17 Feb 2020
Cited by 7 | Viewed by 4421
Abstract
Retinoic acid (RA) was one of the first molecules in the modern era of experimental embryology to be shown capable of generating profound effects on limb development. In this review, we focus on the earliest events of limb development and specifically on the [...] Read more.
Retinoic acid (RA) was one of the first molecules in the modern era of experimental embryology to be shown capable of generating profound effects on limb development. In this review, we focus on the earliest events of limb development and specifically on the role of RA in establishing the domain of cells that will go on to form the limb itself. Although there is some consensus on the role of RA during the earliest stages of limb formation, some controversy remains on the mechanism of RA action and the requirement for RA signaling in forming the hindlimb buds. Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)
Show Figures

Graphical abstract

18 pages, 795 KiB  
Review
Retinoic Acid: A Key Regulator of Lung Development
by Hugo Fernandes-Silva, Henrique Araújo-Silva, Jorge Correia-Pinto and Rute S Moura
Biomolecules 2020, 10(1), 152; https://doi.org/10.3390/biom10010152 - 17 Jan 2020
Cited by 31 | Viewed by 7958
Abstract
Retinoic acid (RA) is a key molecular player in embryogenesis and adult tissue homeostasis. In embryo development, RA plays a crucial role in the formation of different organ systems, namely, the respiratory system. During lung development, there is a spatiotemporal regulation of RA [...] Read more.
Retinoic acid (RA) is a key molecular player in embryogenesis and adult tissue homeostasis. In embryo development, RA plays a crucial role in the formation of different organ systems, namely, the respiratory system. During lung development, there is a spatiotemporal regulation of RA levels that assures the formation of a fully functional organ. RA signaling influences lung specification, branching morphogenesis, and alveolarization by regulating the expression of particular target genes. Moreover, cooperation with other developmental pathways is essential to shape lung organogenesis. This review focuses on the events regulated by retinoic acid during lung developmental phases and pulmonary vascular development; also, it aims to provide a snapshot of RA interplay with other well-known regulators of lung development. Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)
Show Figures

Figure 1

17 pages, 1538 KiB  
Review
Generation of Retinaldehyde for Retinoic Acid Biosynthesis
by Olga V. Belyaeva, Mark K. Adams, Kirill M. Popov and Natalia Y. Kedishvili
Biomolecules 2020, 10(1), 5; https://doi.org/10.3390/biom10010005 - 18 Dec 2019
Cited by 33 | Viewed by 9574
Abstract
The concentration of all-trans-retinoic acid, the bioactive derivative of vitamin A, is critically important for the optimal performance of numerous physiological processes. Either too little or too much of retinoic acid in developing or adult tissues is equally harmful. All-trans [...] Read more.
The concentration of all-trans-retinoic acid, the bioactive derivative of vitamin A, is critically important for the optimal performance of numerous physiological processes. Either too little or too much of retinoic acid in developing or adult tissues is equally harmful. All-trans-retinoic acid is produced by the irreversible oxidation of all-trans-retinaldehyde. Thus, the concentration of retinaldehyde as the immediate precursor of retinoic acid has to be tightly controlled. However, the enzymes that produce all-trans-retinaldehyde for retinoic acid biosynthesis and the mechanisms responsible for the control of retinaldehyde levels have not yet been fully defined. The goal of this review is to summarize the current state of knowledge regarding the identities of physiologically relevant retinol dehydrogenases, their enzymatic properties, and tissue distribution, and to discuss potential mechanisms for the regulation of the flux from retinol to retinaldehyde. Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)
Show Figures

Figure 1

25 pages, 1360 KiB  
Review
New Insights into the Control of Cell Fate Choices and Differentiation by Retinoic Acid in Cranial, Axial and Caudal Structures
by Heidrun Draut, Thomas Liebenstein and Gerrit Begemann
Biomolecules 2019, 9(12), 860; https://doi.org/10.3390/biom9120860 - 11 Dec 2019
Cited by 12 | Viewed by 5249
Abstract
Retinoic acid (RA) signaling is an important regulator of chordate development. RA binds to nuclear RA receptors that control the transcriptional activity of target genes. Controlled local degradation of RA by enzymes of the Cyp26a gene family contributes to the establishment of transient [...] Read more.
Retinoic acid (RA) signaling is an important regulator of chordate development. RA binds to nuclear RA receptors that control the transcriptional activity of target genes. Controlled local degradation of RA by enzymes of the Cyp26a gene family contributes to the establishment of transient RA signaling gradients that control patterning, cell fate decisions and differentiation. Several steps in the lineage leading to the induction and differentiation of neuromesodermal progenitors and bone-producing osteogenic cells are controlled by RA. Changes to RA signaling activity have effects on the formation of the bones of the skull, the vertebrae and the development of teeth and regeneration of fin rays in fish. This review focuses on recent advances in these areas, with predominant emphasis on zebrafish, and highlights previously unknown roles for RA signaling in developmental processes. Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)
Show Figures

Figure 1

20 pages, 1640 KiB  
Review
Retinoic Acid and Germ Cell Development in the Ovary and Testis
by Tsutomu Endo, Maria M. Mikedis, Peter K. Nicholls, David C. Page and Dirk G. de Rooij
Biomolecules 2019, 9(12), 775; https://doi.org/10.3390/biom9120775 - 24 Nov 2019
Cited by 62 | Viewed by 9552
Abstract
Retinoic acid (RA), a derivative of vitamin A, is critical for the production of oocytes and sperm in mammals. These gametes derive from primordial germ cells, which colonize the nascent gonad, and later undertake sexual differentiation to produce oocytes or sperm. During fetal [...] Read more.
Retinoic acid (RA), a derivative of vitamin A, is critical for the production of oocytes and sperm in mammals. These gametes derive from primordial germ cells, which colonize the nascent gonad, and later undertake sexual differentiation to produce oocytes or sperm. During fetal development, germ cells in the ovary initiate meiosis in response to RA, whereas those in the testis do not yet initiate meiosis, as they are insulated from RA, and undergo cell cycle arrest. After birth, male germ cells resume proliferation and undergo a transition to spermatogonia, which are destined to develop into haploid spermatozoa via spermatogenesis. Recent findings indicate that RA levels change periodically in adult testes to direct not only meiotic initiation, but also other key developmental transitions to ensure that spermatogenesis is precisely organized for the prodigious output of sperm. This review focuses on how female and male germ cells develop in the ovary and testis, respectively, and the role of RA in this process. Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)
Show Figures

Figure 1

17 pages, 1566 KiB  
Review
Two Opposing Faces of Retinoic Acid: Induction of Stemness or Induction of Differentiation Depending on Cell-Type
by Belén Mezquita and Cristóbal Mezquita
Biomolecules 2019, 9(10), 567; https://doi.org/10.3390/biom9100567 - 04 Oct 2019
Cited by 23 | Viewed by 5626
Abstract
Stem cells have the capacity of self-renewal and, through proliferation and differentiation, are responsible for the embryonic development, postnatal development, and the regeneration of tissues in the adult organism. Cancer stem cells, analogous to the physiological stem cells, have the capacity of self-renewal [...] Read more.
Stem cells have the capacity of self-renewal and, through proliferation and differentiation, are responsible for the embryonic development, postnatal development, and the regeneration of tissues in the adult organism. Cancer stem cells, analogous to the physiological stem cells, have the capacity of self-renewal and may account for growth and recurrence of tumors. Development and regeneration of healthy tissues and tumors depend on the balance of different genomic and nongenomic signaling pathways that regulate stem cell quiescence, proliferation, and differentiation. During evolution, this balance became dependent on all-trans retinoic acid (RA), a molecule derived from the environmental factor vitamin A. Here we summarize some recent findings on the prominent role of RA on the proliferation of stem and progenitor cells, in addition to its well-known function as an inductor of cell differentiation. A better understanding of the regulatory mechanisms of stemness and cell differentiation by RA may improve the therapeutic options of this molecule in regenerative medicine and cancer. Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)
Show Figures

Graphical abstract

Back to TopTop