Decoding of position in the developing neural tube from antiparallel morphogen gradients.

Marcin Zagorski,Yoji Tabata,Gašper Tkačik,James Briscoe,Tobias Bollenbach,Matthias P Lutolf,Nathalie Brandenberg,Anna Kicheva

doi:10.1126/science.aam5887

Abstract

Like many developing tissues, the vertebrate neural tube is patterned by antiparallel morphogen gradients. To understand how these inputs are interpreted, we measured morphogen signaling and target gene expression in mouse embryos and chick ex vivo assays. From these data, we derived and validated a characteristic decoding map that relates morphogen input to the positional identity of neural progenitors. Analysis of the observed responses indicates that the underlying interpretation strategy minimizes patterning errors in response to the joint input of noisy opposing gradients. We reverse-engineered a transcriptional network that provides a mechanistic basis for the observed cell fate decisions and accounts for the precision and dynamics of pattern formation. Together, our data link opposing gradient dynamics in a growing tissue to precise pattern formation.

Highlights

Like many developing tissues, the vertebrate neural tube is patterned by antiparallel morphogen gradients
The levels of Sonic hedgehog (Shh) and Bone morphogenetic proteins (BMP) signaling as a function of the absolute distance to the source did not change appreciably during the first 30h of development (Fig. 1B, C)
After 30h, the Shh and BMP signaling levels markedly decrease in the middle of the DV axis and the positional error increases to >20 cell diameters (Fig. 1E)

Summary

Introduction

The vertebrate neural tube is patterned by antiparallel morphogen gradients. Neither the Shh, nor the BMP signaling gradient alone provides precise positional information throughout the DV axis. After 30h, the Shh and BMP signaling levels markedly decrease in the middle of the DV axis and the positional error increases to >20 cell diameters (Fig. 1E).

Results

Conclusion