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Pervasive translational regulation of the cell signalling circuitry underlies mammalian development.

Nature communications (2017-02-15)
Kotaro Fujii, Zhen Shi, Olena Zhulyn, Nicolas Denans, Maria Barna
ABSTRACT

The degree and dynamics of translational control during mammalian development remain poorly understood. Here we monitored translation of the mammalian genome as cells become specified and organize into tissues in vivo. This identified unexpected and pervasive translational regulation of most of the core signalling circuitry including Shh, Wnt, Hippo, PI3K and MAPK pathways. We further identify and functionally characterize a complex landscape of upstream open reading frames (uORFs) across 5'-untranslated regions (UTRs) of key signalling components. Focusing on the Shh pathway, we demonstrate the importance of uORFs within the major SHH receptor, Ptch1, in control of cell signalling and neuronal differentiation. Finally, we show that the expression of hundreds of mRNAs underlying critical tissue-specific developmental processes is largely regulated at the translation but not transcript levels. Altogether, this work reveals a new layer of translational control to major signalling components and gene regulatory networks that diversifies gene expression spatially across developing tissues.

MATERIALS
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Product Description

Sigma-Aldrich
2-Mercaptoethanol, for molecular biology, suitable for electrophoresis, suitable for cell culture, BioReagent, 99% (GC/titration)
Sigma-Aldrich
Retinoic acid, ≥98% (HPLC), powder
Sigma-Aldrich
Bovine Serum Albumin, lyophilized powder, γ-irradiated, Globulin Free, BioXtra, suitable for cell culture