Temporal dynamics in the formation and interpretation of Nodal and BMP morphogen gradients

Abstract

One of the most powerful ideas in developmental biology has been that of the morphogen gradient. In the classical view, a signaling molecule is produced at a local source from where it diffuses, resulting in graded levels across the tissue. This gradient provides positional information, with thresholds in the level of the morphogen determining the position of different cell fates. While experimental studies have uncovered numerous potential morphogens in biological systems, it is becoming increasingly apparent that one important feature, not captured in the simple model, is the role of time in both the formation and interpretation of morphogen gradients. We will focus on two members of the transforming growth factor-β family that are known to play a vital role as morphogens in early vertebrate development: the Nodals and the bone morphogenetic proteins (BMPs). Primarily drawing on the early zebrafish embryo, we will show how recent studies have demonstrated the importance of feedback and other interactions that evolve through time, in shaping morphogen gradients. We will further show how rather than simply reading out levels of a morphogen, the duration of ligand exposure can be a crucial determinant of how cells interpret morphogens, in particular through the unfolding of downstream transcriptional events and in their interactions with other pathways.

Keywords: BMP; Drosophila; Morphogen gradient; Nodal; Smad; Zebrafish.