Developmental Signals - Retinoic acid

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Introduction

All-trans retinoic acid (atRA)
Model for retinoid acid in olfactory development[1]


All-trans retinoic acid (atRA) is the transcriptionally active product of vitamin A and is known to play many roles in regulating embryo development. In the adult retinoid acid has additional signalling roles including spermatozoa maturation.


The compound has been used extensively postnatally in therapeutic treatments, for example in skin disease. As this compound also acts as a developmental signal, it has known teratogenic effects[2][3] following maternal to conceptus transfer.


Retinoic Acid Links: Retinoic acid | Category:Retinoic acid | Molecular Development


Factor Links: hCG | BMP | Sonic hedgehog | HOX | FGF | Nanog | Nodal | Notch | FOX | PAX | Retinoic acid | SIX | Slit2/Robo1 | Sox | TBX | TGF-beta | VEGF | WNT | Hippo | NGF | Category:Molecular
| Category:Retinoic acid | Abnormal Development

Some Recent Findings

  • Cyp26 Enzymes Facilitate Second Heart Field Progenitor Addition and Maintenance of Ventricular Integrity[4] "Although retinoic acid (RA) teratogenicity has been investigated for decades, the mechanisms underlying RA-induced outflow tract (OFT) malformations are not understood. Here, we show zebrafish embryos deficient for Cyp26a1 and Cyp26c1 enzymes, which promote RA degradation, have OFT defects resulting from two mechanisms: first, a failure of second heart field (SHF) progenitors to join the OFT, instead contributing to the pharyngeal arch arteries (PAAs), and second, a loss of first heart field (FHF) ventricular cardiomyocytes due to disrupted cell polarity and extrusion from the heart tube." Zebrafish Development | Cardiovascular Abnormalities
  • Retinoic acid signaling and neuronal differentiation[5] "The identification of neurological symptoms caused by vitamin A deficiency pointed to a critical, early developmental role of vitamin A and its metabolite, retinoic acid (RA). The ability of RA to induce post-mitotic, neural phenotypes in various stem cells, in vitro, served as early evidence that RA is involved in the switch between proliferation and differentiation. In vivo studies have expanded this "opposing signal" model, and the number of primary neurons an embryo develops is now known to depend critically on the levels and spatial distribution of RA. The proneural and neurogenic transcription factors that control the exit of neural progenitors from the cell cycle and allow primary neurons to develop are partly elucidated, but the downstream effectors of RA receptor (RAR) signaling (many of which are putative cell cycle regulators) remain largely unidentified. The molecular mechanisms underlying RA-induced primary neurogenesis in anamniote embryos are starting to be revealed; however, these data have been not been extended to amniote embryos. There is growing evidence that bona fide RARs are found in some mollusks and other invertebrates, but little is known about their necessity or functions in neurogenesis. One normal function of RA is to regulate the cell cycle to halt proliferation, and loss of RA signaling is associated with dedifferentiation and the development of cancer. Identifying the genes and pathways that mediate cell cycle exit downstream of RA will be critical for our understanding of how to target tumor differentiation. Overall, elucidating the molecular details of RAR-regulated neurogenesis will be decisive for developing and understanding neural proliferation-differentiation switches throughout development."
  • Visualization of an endogenous retinoic acid gradient across embryonic development[6] "In vertebrate development, the body plan is determined by primordial morphogen gradients that suffuse the embryo. Retinoic acid (RA) is an important morphogen involved in patterning the anterior-posterior axis of structures, including the hindbrain and paraxial mesoderm. RA diffuses over long distances, and its activity is spatially restricted by synthesizing and degrading enzymes. ...Live imaging of endogenous concentration gradients across embryonic development will allow the precise assignment of molecular mechanisms to developmental dynamics and will accelerate the application of approaches based on morphogen gradients to tissue engineering and regenerative medicine." Zebrafish Development
More recent papers  
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Search term: Embryo Retinoic acid | Images

Yehuda Shabtai, Natalie Shukrun, Abraham Fainsod ADHFe1: a novel enzyme involved in retinoic acid-dependent Hox activation. Int. J. Dev. Biol.: 2017, 61(3-4-5);303-310 PubMed 28621427

Aldert H Piersma, Ellen V Hessel, Yvonne C Staal Retinoic acid in developmental toxicology: teratogen, morphogen and biomarker. Reprod. Toxicol.: 2017; PubMed 28591664

Bony De Kumar, Hugo J Parker, Mark E Parrish, Jeffrey J Lange, Brian D Slaughter, Jay R Unruh, Ariel Paulson, Robb Krumlauf Dynamic regulation of Nanog and stem cell-signaling pathways by Hoxa1 during early neuro-ectodermal differentiation of ES cells. Proc. Natl. Acad. Sci. U.S.A.: 2017; PubMed 28584089

Qin-Xiao Hu, Xue-Dong Li, Peng Xie, Chu-Cheng Wu, Gui-Zhou Zheng, Fei-Xiang Lin, Da Xie, Qi-Hao Zhang, De-Zhong Liu, Yun-Guo Wang, Bo Chang, Shi-Xin Du All-trans-retinoic acid activates SDF-1/CXCR4/ROCK2 signaling pathway to inhibit chondrogenesis. Am J Transl Res: 2017, 9(5);2296-2305 PubMed 28559980

Syed Mohmad Shah, Suresh Kumar Singla, Prabhat Palta, Radhey Sham Manik, Manmohan Singh Chauhan Retinoic acid induces differentiation of buffalo (Bubalus bubalis) embryonic stem cells into germ cells. Gene: 2017; PubMed 28526652

Organ Expression

Rar gene expression.jpg

Summary of Rar gene expression patterns in mouse developing organ systems.[7]

Endoderm

Chicken antero-posterior endoderm patterning cartoon

Chicken antero-posterior endoderm patterning[8]


Links: Endoderm | Chicken Development

Fetal Gonad

Human fetal gonad retinoid receptor expression.jpg

Immunohistochemical localisation of retinoid receptor expression in the human fetal gonad[9]


Neural

Model retinoic acid extracellular signal-regulated kinase and Wnt pathway interactions.jpg

Model retinoic acid extracellular signal-regulated kinase and Wnt pathway interactions[10]

Mouse embryo cortex radial expansion.jpg

RA Is Not Required for Radial Expansion of the Embryonic Cortex

References

  1. Marie Paschaki, Laura Cammas, Yuko Muta, Yoko Matsuoka, Siu-Shan Mak, Monika Rataj-Baniowska, Valérie Fraulob, Pascal Dollé, Raj K Ladher Retinoic acid regulates olfactory progenitor cell fate and differentiation. Neural Dev: 2013, 8;13 PubMed 23829703 | Neural Dev.
  2. M D Collins, G E Mao Teratology of retinoids. Annu. Rev. Pharmacol. Toxicol.: 1999, 39;399-430 PubMed 10331090
  3. G Tzimas, H Nau The role of metabolism and toxicokinetics in retinoid teratogenesis. Curr. Pharm. Des.: 2001, 7(9);803-31 PubMed 11375780
  4. Ariel B Rydeen, Joshua S Waxman Cyp26 Enzymes Facilitate Second Heart Field Progenitor Addition and Maintenance of Ventricular Integrity. PLoS Biol.: 2016, 14(11);e2000504 PubMed 27893754
  5. Amanda Janesick, Stephanie Cherie Wu, Bruce Blumberg Retinoic acid signaling and neuronal differentiation. Cell. Mol. Life Sci.: 2015; PubMed 25558812
  6. Satoshi Shimozono, Tadahiro Iimura, Tetsuya Kitaguchi, Shin-Ichi Higashijima, Atsushi Miyawaki Visualization of an endogenous retinoic acid gradient across embryonic development. Nature: 2013, 496(7445);363-6 PubMed 23563268
  7. Pascal Dollé Developmental expression of retinoic acid receptors (RARs). Nucl Recept Signal: 2009, 7;e006 PubMed 19471585
  8. 19516907</pubmed>| PLoS One.
  9. Childs AJ, Cowan G, Kinnell HL, Anderson RA, Saunders PTK (2011) Retinoic Acid Signalling and the Control of Meiotic Entry in the Human Fetal Gonad. PLoS ONE 6(6): e20249. PMID 21674038 | PLoS One
  10. Jianfeng Lu, Li Tan, Ping Li, Hui Gao, Bo Fang, Shoudong Ye, Zhe Geng, Ping Zheng, Houyan Song All-trans retinoic acid promotes neural lineage entry by pluripotent embryonic stem cells via multiple pathways. BMC Cell Biol.: 2009, 10;57 PubMed 19642999


Articles

Pina Bozzo, Angela Chua-Gocheco, Adrienne Einarson Safety of skin care products during pregnancy. Can Fam Physician: 2011, 57(6);665-7 PubMed 21673209

| Can Fam Physician

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Cite this page: Hill, M.A. 2017 Embryology Developmental Signals - Retinoic acid. Retrieved June 26, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Signals_-_Retinoic_acid

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© Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G