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Robustness of retinoic acid regulatory homeostasis during early development (RNA-seq)

ABSTRACT: Retinoic acid (RA) is a central developmental signal whose perturbation results in teratogenic outcomes. RA are tightly regulated during early embryonic development to achieve fine-tuning of the instructive and permissive signals regulating multiple developmental processes including head formation. We aim to identify the key mechanisms underlying the homeostatic regulation and tuning of the retinoic acid signaling levels, the disruption of which in the head lead to wide ranging developmental malformations including microcephaly and other craniofacial defects. We performed transient physiological RA signaling disturbances during Xenopus laevis embryogenesis followed by kinetic RNAseq analysis of the recovery at multiple time points.

ORGANISM(S): Xenopus laevis

PROVIDER: GSE154399 | GEO | 2021/09/29

REPOSITORIES: GEO

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Project description:This is the simple model without diffusion described in th epublication Sharp developmental thresholds defined through bistability by antagonistic gradients of retinoic acid and FGF signaling. Goldbeter A, Gonze D, Pourquié O. Dev Dyn. 2007 Jun;236(6):1495-508. PMID: 17497689, doi:10.1016/j.jtbi.2008.01.006 Abstract: The establishment of thresholds along morphogen gradients in the embryo is poorly understood. Using mathematical modeling, we show that mutually inhibitory gradients can generate and position sharp morphogen thresholds in the embryonic space. Taking vertebrate segmentation as a paradigm, we demonstrate that the antagonistic gradients of retinoic acid (RA) and Fibroblast Growth Factor (FGF) along the presomitic mesoderm (PSM) may lead to the coexistence of two stable steady states. Here, we propose that this bistability is associated with abrupt switches in the levels of FGF and RA signaling, which permit the synchronized activation of segmentation genes, such as mesp2, in successive cohorts of PSM cells in response to the segmentation clock, thereby defining the future segments. Bistability resulting from mutual inhibition of RA and FGF provides a molecular mechanism for the all-or-none transitions assumed in the "clock and wavefront" somitogenesis model. Given that mutually antagonistic signaling gradients are common in development, such bistable switches could represent an important principle underlying embryonic patterning. Originally created by libAntimony v1.4 (using libSBML 3.4.1) This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. For more information see the terms of use. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

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Robustness of retinoic acid regulatory homeostasis during early development (RNA-seq)

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