Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.07.15.203794v1?rss=1
Authors: Parihar, M., Bendelac-Kapon, L., Gur, M., Belorkar, A., Achanta, S., Kinberg, K., Vadigepalli, R., Fainsod, A.
Abstract:
Retinoic acid (RA) is a central developmental signal whose perturbation results in teratogenic outcomes. We performed transient physiological RA signaling disturbances during embryogenesis followed by kinetic RNAseq and high-throughput qPCR analysis of the recovery. Unbiased comparative pattern analysis identified the RA network as a key differentially regulated module aimed at achieving RA signaling robustness. We analyzed this module using a principal curve-based approach determining clutch-wise variability, and organized the results into a robustness efficiency matrix comparing the shifts in RA feedback regulation and hox gene expression. We found that feedback autoregulation was sensitive to the direction of the RA perturbation: RA knock-down exhibited an upper response limit, whereas RA addition did not activate a feedback response below a threshold. These results suggest an asymmetric capacity for robust feedback control of RA signal during early development based on genetic polymorphisms, likely a significant contributor to the manifestation of developmental defects.
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