Computational analysis of BMP gradients in dorsal-ventral patterning of the zebrafish embryo

Yong-Tao Zhang,Arthur D Lander,Qing Nie

doi:10.1016/j.jtbi.2007.05.026

Yong-Tao Zhang, Arthur D Lander + Show 1 more

Open Access

https://doi.org/10.1016/j.jtbi.2007.05.026

Copy DOI

Abstract

The genetic network controlling early dorsal-ventral (DV) patterning has been extensively studied and modeled in the fruit fly Drosophila. This patterning is driven by signals coming from bone morphogenetic proteins (BMPs), and regulated by interactions of BMPs with secreted factors such as the antagonist short gastrulation (Sog). Experimental studies suggest that the DV patterning of vertebrates is controlled by a similar network of BMPs and antagonists (such as Chordin, a homologue of Sog), but differences exist in how the two systems are organized, and a quantitative comparison of pattern formation in them has not been made. Here, we develop a computational model in three dimensions of the zebrafish embryo and use it to study molecular interactions in the formation of BMP morphogen gradients in early DV patterning. Simulation results are presented on the dynamics BMP gradient formation, the cooperative action of two feedback loops from BMP signaling to BMP and Chordin synthesis, and pattern sensitivity with respect to BMP and Chordin dosage. Computational analysis shows that, unlike the case in Drosophila, synergy of the two feedback loops in the zygotic control of BMP and Chordin expression, along with early initiation of localized Chordin expression, is critical for establishment and maintenance of a stable and appropriate BMP gradient in the zebrafish embryo.

Highlights

The proper functioning of tissues and organs requires that each cell differentiates appropriately for its position
Is the transient, localized expression of a bone morphogenetic proteins (BMPs) inhibitor such as chordin essential for producing a stable BMP gradient in vertebrate embryos? Are synergistic feedback loops required for maintaining the gradient? What are the specific roles of those feedbacks? How do the geometry, size, and developmental pace of typical vertebrate embryos interact with forming BMP gradients? In this paper, we study these questions by computational analysis of a mathematical model for zebrafish embryos between the end of blastula stage and the beginning of gastrulation, when a DV gradient of bmp transcripts is most prominent (Hammerschmidt and Mullins, 2002)
It is noted that the initial local production of Chordin around the dorsal organizer region leads to a coarse gradient of occupied BMP receptors

Summary

Introduction

The proper functioning of tissues and organs requires that each cell differentiates appropriately for its position. The positional information that instructs cells about their prospective fates is conveyed by concentration gradients of morphogens bound to cellular receptors. Morphogens are signaling molecules that, when bound to receptors, assign different cell fates at different concentrations (Teleman et al, 2001; Wolpert et al, 2002). Present address: Department of Mathematics, University of Notre Dame, 255 Hurley Hall, Notre Dame, IN 46556-4618, USA.

Objectives

Results

Conclusion