Details

Autor(en) / Beteiligte

• van Boxtel, Antonius L.
• Chesebro, John E.
• Heliot, Claire
• Ramel, Marie-Christine
• Stone, Richard K.
• Hill, Caroline S.

Titel

A Temporal Window for Signal Activation Dictates the Dimensions of a Nodal Signaling Domain

Ist Teil von

• Developmental cell, 2015-10, Vol.35 (2), p.175-185

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Morphogen signaling is critical for the growth and patterning of tissues in embryos and adults, but how morphogen signaling gradients are generated in tissues remains controversial. The morphogen Nodal was proposed to form a long-range signaling gradient via a reaction-diffusion system, on the basis of differential diffusion rates of Nodal and its antagonist Lefty. Here we use a specific zebrafish Nodal biosensor combined with immunofluorescence for phosphorylated Smad2 to demonstrate that endogenous Nodal is unlikely to diffuse over a long range. Instead, short-range Nodal signaling activation in a temporal window is sufficient to determine the dimensions of the Nodal signaling domain. The size of this temporal window is set by the differentially timed production of Nodal and Lefty, which arises mainly from repression of Lefty translation by the microRNA miR-430. Thus, temporal information is transformed into spatial information to define the dimensions of the Nodal signaling domain and, consequently, to specify mesendoderm. [Display omitted] •Nodal signals exclusively in cells that express both ligand and antagonist•Lefty1 protein levels are low until the onset of gastrulation•miR-430 represses Lefty translation, creating a signal activation window•Duration of Nodal pathway activation translates into graded signaling van Boxtel et al. show how temporal information in the zebrafish embryo is transformed into a spatial pattern. They demonstrate that the dimensions of the earliest Nodal signaling domain are determined by a temporal signal activation window created by a microRNA-mediated delay in the translation of Lefty, a Nodal antagonist.