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 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 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 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.

scholarly journals Administration of All-Trans Retinoic Acid to Pregnant Sows Improves the Developmental Defects of Hoxa1−/− Fetal Pigs

2021 ◽  
Vol 7 ◽  
Author(s):  
Haimei Zhou ◽  
Yixin Chen ◽  
Yongqiang Hu ◽  
Shan Gao ◽  
Wei Lu ◽  
...  
Keyword(s):  
Body Weight ◽  
Retinoic Acid ◽  
Control Group ◽  
External Ear ◽  
Developmental Defects ◽  
Neonatal Piglets ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Canal Atresia ◽  
Fetal Pig

Hoxa1 mutation adversely affect fetal pig development, but whether all-trans retinoic acid (ATRA) administration to Hoxa1+/− pregnant sows can improve Hoxa1−/− fetal pig development defects has not been reported. A total of 24 healthy Hoxa1+/− sows were mated with a healthy Hoxa1+/− boar and randomly assigned to one control group and nine experiment groups. ATRA was orally administered to pregnant sows at the doses of 0, 4, 5, or 6 mg/kg maternal body weight on 12, 13, and 14 days post coitum (dpc), respectively, and a total of 146 live piglets were delivered including 37 Hoxa1−/− piglets and 109 non-Hoxa1−/− piglets. Results indicated that Hoxa1−/− piglets delivered by sows in control group had bilateral microtia, canal atresia and ear's internal defects, and had lower birth liveweight and external ear score than non-Hoxa1−/− neonatal piglets (P < 0.05). Maternal administration with ATRA can effectively correct the development defects of Hoxa1−/− fetal pigs, Hoxa1−/− neonatal piglets delivered by sows administered ATRA at a dose of 4 mg/kg body weight on 14 dpc had higher birth liveweight (P > 0.05) and higher scores of external ear (P < 0.05) compared to Hoxa1−/− neonatal piglets from the control group, but had no significantly difference in terms of birth liveweight and external ear integrity than non-Hoxa1−/− piglets from the control group (P > 0.05). The time of ATRA administration significantly affected Hoxa1−/− fetal development (P < 0.05). Administration of ATRA to Hoxa1+/− pregnant sows at 4 mg/kg body weight on 14 dpc can effectively improve the birth liveweight and ear defects of Hoxa1−/− piglets.

Immunocytochemical methodology for the localization of neuronal antigens at the ultrastructural level

1990 ◽  
Vol 48 (3) ◽  
pp. 876-877
Author(s):  
Jorge Pecci Saavedra ◽  
Mark Connaughton ◽  
Juan José López ◽  
Alicia Brusco
Keyword(s):  
Spinal Cord ◽  
Substantia Nigra ◽  
Polyclonal Antibodies ◽  
Ultrastructural Level ◽  
Point Of View ◽  
Nerve Tissue ◽  
Tissue Fixation ◽  
Optimal Conditions ◽  
Interpeduncular Nucleus ◽  
Technical Point

The use of antibodies as labels for the localization of specific molecules in the nervous systan has been extensively applied in recent years. Both monoand polyclonal antibodies or antisera have been employed. The knowledge of the organization of neuronal connectivities, gliovascular relationships, glioneuronal relationships and other features of nerve tissue has greatly increased.A number of areas of the nervous systan have been analyzed in our laboratory, including the nuclei of the raphe system, the reticular formation, interpeduncular nucleus, substantia nigra, caudate nucleus, putamen, pallidum, spinal cord, pineal gland and others.From a technical point of view, a number of variables needed to be taken into account in order to obtain reliable and reproducible results. The design of the optimal conditions of tissue fixation, embedding, sectioning, dilution of antibodies, and adaptation of Sternberger PAP technique were sane of the parameters taken into account to optimize the results. It is critical that each step of the technique be defined for each particular case.

Diagnostic evaluation of the substantia nigra

1996 ◽  
Vol 22 (3) ◽  
pp. 228-232 ◽  
Author(s):  
D. A. McRitchie ◽  
G. M. Halliday ◽  
R. Pamphlett
Keyword(s):  
Substantia Nigra ◽  
Diagnostic Evaluation
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