Transcriptome analysis by RNA-Seq reveals tissue specific regulatory pathways underlying crosstalk between thyroid Hormone and glucocorticoids signaling

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 389-413-Signaling and Transcriptional Control in Endocrine Systems
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-391
Laurent M. Sachs*1, Alexis Grimaldi1, Corinne Bluegon2, Adeline Couvé2 and Nicolas Buisine1
1Muséum National d'Histoire Naturelle, PARIS, France, 2ENS, PARIS, France

Available data suggests that post-embryonic remodeling period governed by Thyroid Hormones (TH) and Glucocorticoids (GC) is an ancestral feature of chordates. The disruption of these two endocrine pathways during the post-embryonic period, as a consequence of environmental cues or clinical effects, can have deleterious effects on human health over lifespan (mental, cardiovascular, and metabolism associated diseases, cancer, behavior and adverse effect on the overall quality of life). Yet, the molecular detail of the crosstalk between TH and GC is poorly known. The characterization of the regulatory programs induced by TH and GC and the molecular mechanisms that control these programs will help understand how these two endocrine signals control cell fate. We use amphibian metamorphosis to dissect the regulatory pathways of genes and genetic networks underlying TH and GC signaling in vivo in vertebrate systems. Amphibian metamorphosis is the process by which an aquatic tadpole switches to an air-breathing adult. This complex process involves both apoptosis (tail resorption, brain and intestine remodeling) and cellular proliferation (limb growth, brain and intestine remodeling). Metamorphosis is initiated by a single signal (TH) but is modulated by multiple physiological and external inputs. GC signaling is a natural component of physiological processes that are involved in metamorphosis. It is is also an antenna for environmental inputs aimed at modulating the timing and the molecular and cellular processes during metamorphosis. These two hormones are pivotal to the transcriptional regulation of key genes. In order to probe for the molecular determinants of the effects of TH and GC on metamorphosis, we analyzed the modulation of gene expression in tadpoles exposed to a simulated stress by systematic sequencing of the transcripts (RNA-Seq) present in tail-fin epidermis and in developing hind limbs, two tissues presenting different cell fate during metamorphosis (respectively regression and morphogenesis). We found that each hormone was able to independently promote mostly non-overlapping cellular processes. In contrast, both hormones together could modify the expression levels of a specific set of several hundreds of genes (depending on the tissue), which could affect adaptability to challenging environments. Our results carried out in Xenopus tropicalis may shed a new light on stress response and crosstalk between signaling pathways among vertebrates.

Nothing to Disclose: LMS, AG, CB, AC, NB

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Sources of Research Support: European Union IDEAL (project n°259679) and Young researcher ANR TRIGGER