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

Dev Cell. 2015 Oct 26;35(2):175-85. doi: 10.1016/j.devcel.2015.09.014.

Abstract

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.

Keywords: Lefty; Nodal; mesendoderm; miR-430; morphogen; temporal signal activation window; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biosensing Techniques
  • Body Patterning / genetics*
  • Gene Expression Regulation, Developmental
  • Left-Right Determination Factors / biosynthesis
  • Left-Right Determination Factors / genetics*
  • MicroRNAs / genetics*
  • Nodal Protein / genetics*
  • Nodal Protein / metabolism
  • Smad2 Protein / biosynthesis
  • Smad2 Protein / genetics
  • Zebrafish / genetics
  • Zebrafish / growth & development
  • Zebrafish Proteins / biosynthesis
  • Zebrafish Proteins / genetics*

Substances

  • Left-Right Determination Factors
  • MicroRNAs
  • Mirn430 microRNA, zebrafish
  • Nodal Protein
  • Smad2 Protein
  • Zebrafish Proteins
  • lft1 protein, zebrafish
  • smad2 protein, zebrafish