scholarly journals Retinoic acid-induced developmental defects are mediated by RARbeta/RXR heterodimers in the pharyngeal endoderm

Development ◽  
2003 ◽  
Vol 130 (10) ◽  
pp. 2083-2093 ◽  
Author(s):  
N. Matt
Keyword(s):  
Retinoic Acid ◽  
Developmental Defects ◽  
Pharyngeal Endoderm

scholarly journals Endoderm Morphogenesis Reveals Integration of Distinct Processes in the Development and Evolution of Pharyngeal Arches

2018 ◽  
Author(s):  
Kazunori Okada ◽  
Hiroshi Wada ◽  
Shinji Takada
Keyword(s):  
Retinoic Acid ◽  
Comparative Analysis ◽  
Retinoic Acid Signaling ◽  
Pharyngeal Arches ◽  
Developmental Defects ◽  
Pharyngeal Endoderm ◽  
Development And Evolution

ABSTRACTThe vertebrate pharyngeal arches (PAs) are established by a combination of two styles of segmentation; the most anterior 2 PAs are simultaneously but the others are sequentially formed. However, the mechanism underlying their coexistence is unclear. Here, we show that the simultaneous and sequential segmentation discretely proceeded, respectively, but were finally integrated at the second PP (PP2), by dynamic morphogenesis of pharyngeal endoderm in the zebrafish. The coordination of these 2 distinct processes appears to be common in the PA development of many vertebrates, in which specific developmental defects posterior to the PP2 are caused by mutations of particular genes or perturbation of retinoic acid signaling. Surprisingly, comparative analysis of PA segmentation showed that the combinatorial styles of PA development is present in shark but not in lamprey, suggesting that PA segmentation was modified in the stem gnathostomes corresponding to the drastic pharyngeal innovations, such as PA2-derived opercular.

scholarly journals Asymmetric robustness in the feedback control of the retinoic acid network response to environmental disturbances

2020 ◽  
Author(s):  
Madhur Parihar ◽  
Liat Bendelac-Kapon ◽  
Michal Gur ◽  
Abha Belorkar ◽  
Sirisha Achanta ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Feedback Control ◽  
Genetic Polymorphisms ◽  
Pattern Analysis ◽  
Environmental Changes ◽  
Feedback Regulation ◽  
Response Threshold ◽  
Developmental Defects ◽  
Regulatory Pathways ◽  
Qpcr Analysis

ABSTRACTRobustness is a characteristic of regulatory pathways to ensure signal consistency in light of environmental changes or genetic polymorphisms. The retinoic acid (RA) pathway is a central developmental and tissue homeostasis regulatory signal, strongly dependent on nutritional sources of retinoids and affected by exogenous chemicals. We performed transient physiological RA signaling disturbances during embryogenesis followed by kinetic transcriptomic and high-throughput qPCR analysis of the recovery. Unbiased pattern analysis identified the RA metabolic network as the main regulated module aimed at achieving signaling robustness. We used a principal trajectory-based analysis of the clutch-dependent variability and organized the results into a robustness efficiency matrix comparing the RA feedback regulation and hox gene expression (RA targets). We found the feedback autoregulation to be sensitive to the direction of the RA perturbation: RA knockdown exhibited an upper response threshold, whereas RA addition did not activate a feedback response below a minimum threshold. These results demonstrate an asymmetric capacity for robust feedback control of the RA signal during early embryogenesis, probably based on genetic polymorphisms, likely a significant contributor to the manifestation of developmental defects.

scholarly journals Retinoic acid counteracts developmental defects in the substantia nigra caused by Pitx3 deficiency

Development ◽  
2007 ◽  
Vol 134 (14) ◽  
pp. 2673-2684 ◽  
Author(s):  
F. M. J. Jacobs ◽  
S. M. Smits ◽  
C. W. Noorlander ◽  
L. von Oerthel ◽  
A. J. A. van der Linden ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Substantia Nigra ◽  
Developmental Defects

scholarly journals A Retinoic Acid Responsive Hoxa3 Transgene Expressed in Embryonic Pharyngeal Endoderm, Cardiac Neural Crest and a Subdomain of the Second Heart Field

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e27624 ◽  
Author(s):  
Nata Y. S.-G. Diman ◽  
Sophie Remacle ◽  
Nicolas Bertrand ◽  
Jacques J. Picard ◽  
Stéphane Zaffran ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Neural Crest ◽  
Cardiac Neural Crest ◽  
Second Heart Field ◽  
Pharyngeal Endoderm ◽  
Heart Field

Expression of AmphiHox-1 and AmphiPax-1 in amphioxus embryos treated with retinoic acid: insights into evolution and patterning of the chordate nerve cord and pharynx

Development ◽  
1996 ◽  
Vol 122 (6) ◽  
pp. 1829-1838 ◽  
Author(s):  
L.Z. Holland ◽  
N.D. Holland
Keyword(s):  
Retinoic Acid ◽  
Neural Crest ◽  
Nerve Cord ◽  
Hox Genes ◽  
Expression Patterns ◽  
Expression Domain ◽  
Craniofacial Malformations ◽  
Pharyngeal Arches ◽  
Pharyngeal Endoderm ◽  
Cerebral Vesicle

Excess all-trans retinoic acid (RA) causes severe craniofacial malformations in vertebrate embryos: pharyngeal arches are fused or absent, and a rostrad expansion of Hoxb-1 expression in the hindbrain shows that anterior rhombomeres are homeotically respecified to a more posterior identity. As a corollary, neural crest migration into the pharyngeal arches is abnormal. We administered excess RA to developing amphioxus, the closest invertebrate relative of the vertebrates and thus a key organism for understanding evolution of the vertebrate body plan. In normal amphioxus, the nerve cord has only a slight anterior swelling, the cerebral vesicle, and apparently lacks migratory neural crest. Nevertheless, excess RA similarly affects amphioxus and vertebrates. The expression domain of AmphiHox-1 (homologous to mouse Hoxb-1) in the amphioxus nerve cord is also extended anteriorly. For both the amphioxus and mouse genes, excess RA causes either (1) continuous expression throughout the preotic hindbrain (mouse) and from the level of somite 7 to the anterior end of the nerve cord (amphioxus) or (2) discontinuous expression with a gap in rhombomere 3 (mouse) and a gap at the posterior end of the cerebral vesicle (amphioxus). A comparison of these expression patterns suggests that amphioxus has a homolog of the vertebrate hindbrain, both preotic and postotic. Although RA alters the expression of AmphiHox-1 expression in the amphioxus nerve cord, it does not alter the expression of AmphiHox-1 in presomitic mesoderm or of alkali myosin light chain (AmphiMlc-alk) in somites, and the axial musculature and notochord develop normally. The most striking morphogenetic effect of RA on amphioxus larvae is the failure of mouth and gill slits to form. In vertebrates effects of excess RA on pharyngeal development have been attributed solely to the abnormal migratory patterns of Hox-expressing cranial neural crest cells. This cannot be true for amphioxus because of the lack of migratory neural crest. Furthermore, expression of Hox genes in pharyngeal tissues of amphioxus has not yet been detected. However, the absence of gill slits in RA-treated amphioxus embryos correlates with an RA-induced failure of AmphiPax-1 to become down-regulated in regions of pharyngeal endoderm that would normally fuse with the overlying ectoderm. In vertebrates, RA might similarly act via Pax-1/9, also expressed in pharyngeal endoderm, to impair pharyngeal patterning.

scholarly journals Retinoic acid is required for endodermal pouch morphogenesis and not for pharyngeal endoderm specification

2006 ◽  
Vol 235 (10) ◽  
pp. 2695-2709 ◽  
Author(s):  
Daniel Kopinke ◽  
Joshua Sasine ◽  
Jennifer Swift ◽  
W. Zac Stephens ◽  
Tatjana Piotrowski
Keyword(s):  
Retinoic Acid ◽  
Pharyngeal Endoderm

scholarly journals Thermal proteome profiling in zebrafish reveals effects of napabucasin on retinoic acid metabolism

2020 ◽  
pp. mcp.RA120.002273
Author(s):  
Niels M Leijten ◽  
Petra Bakker ◽  
Herman P. Spaink ◽  
Jeroen den Hertog ◽  
Simone Lemeer
Keyword(s):  
Retinoic Acid ◽  
Zebrafish Embryo ◽  
Acid Metabolism ◽  
Zebrafish Embryos ◽  
Developmental Defects ◽  
Protein Targets ◽  
Proteome Profiling ◽  
Stat3 Signaling

Thermal proteome profiling (TPP) allows for the unbiased detection of drug – target protein engagements in vivo. Traditionally, one cell type is used for TPP studies, with the risk of missing important differentially expressed target proteins. The use of whole organisms would circumvent this problem. Zebrafish embryos are amenable to such an approach. Here, we used TPP on whole zebrafish embryo lysate to identify protein targets of napabucasin, a compound that may affect Signal transducer and activator of transcription 3 (Stat3) signaling through an ill-understood mechanism. In zebrafish embryos, napabucasin induced developmental defects consistent with inhibition of Stat3 signaling. TPP profiling showed no distinct shift in Stat3 upon napabucasin treatment, but effects were detected on the oxidoreductase, Pora, which might explain effects on Stat3 signaling. Interestingly, thermal stability of several aldehyde dehydrogenases (Aldhs) was affected. Moreover, napabucasin activated ALDH enzymatic activity in vitro. Aldhs have crucial roles in retinoic acid metabolism and functionally we validated napabucasin-mediated activation of the retinoic acid pathway in zebrafish in vivo. We conclude that TPP profiling in whole zebrafish embryo lysate is feasible and facilitates direct correlation of in vivo effects of small molecule drugs with their protein targets.

scholarly journals Retinoic acid is detected at relatively high levels in the CNS of adult rats

2002 ◽  
Vol 282 (3) ◽  
pp. E672-E678 ◽  
Author(s):  
Elizabeth A. Werner ◽  
Hector F. Deluca
Keyword(s):  
Spinal Cord ◽  
Retinoic Acid ◽  
Organic Phase ◽  
Adult Brain ◽  
Cellular Growth ◽  
Adult Rats ◽  
Developmental Defects ◽  
All Trans Retinoic Acid ◽  
And Function ◽  
The Brain

Retinoic acid (RA) is essential for cellular growth and differentiation in developing and adult animals. The central nervous system (CNS) suffers developmental defects if embryonic levels of RA are too high or too low. The production and function of RA in adult brain are unclear. We report that RA is present throughout the brain and spinal cord of adult, vitamin A-deficient (VAD) rats treated with a physiological amount of all- trans-retinol. The hippocampus/cortex contained the highest proportion of RA in the brain (27.2 ± 2.9% of the organic phase radioactivity, and 23.5 ± 0.8% of the organic phase radioactivity extracted from spinal cord was RA). RA comprises a higher proportion of the retinoid pool in the CNS compared with amounts reported in other target tissues (E Werner and HF DeLuca. Arch Biochem Biophys 393: 262–270, 2001). However, RA is not preferentially transported from the blood to the brain. There were 2.90 ± 0.20 fmol RA/g tissue transported to the brain of VAD rats treated with 2.00 nmol [20-3H]all- trans-retinoic acid, but higher amounts of RA were delivered to the liver, testis, and spleen. Because RA is not transported preferentially to brain, this tissue likely synthesizes RA more efficiently than other target tissues.

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