Finding Missing Interactions of the Arabidopsis thaliana Root Stem Cell Niche Gene Regulatory Network

Eugenio Azpeitia,Luis Mendoza,Mariana Benítez,Elena R Alvarez-Buylla,Nathan Weinstein

doi:10.3389/fpls.2013.00110

Abstract

Over the last few decades, the Arabidopsis thaliana root stem cell niche (RSCN) has become a model system for the study of plant development and stem cell niche dynamics. Currently, many of the molecular mechanisms involved in RSCN maintenance and development have been described. A few years ago, we published a gene regulatory network (GRN) model integrating this information. This model suggested that there were missing components or interactions. Upon updating the model, the observed stable gene configurations of the RSCN could not be recovered, indicating that there are additional missing components or interactions in the model. In fact, due to the lack of experimental data, GRNs inferred from published data are usually incomplete. However, predicting the location and nature of the missing data is a not trivial task. Here, we propose a set of procedures for detecting and predicting missing interactions in Boolean networks. We used these procedures to predict putative missing interactions in the A. thaliana RSCN network model. Using our approach, we identified three necessary interactions to recover the reported gene activation configurations that have been experimentally uncovered for the different cell types within the RSCN: (1) a regulation of PHABULOSA to restrict its expression domain to the vascular cells, (2) a self-regulation of WOX5, possibly by an indirect mechanism through the auxin signaling pathway, and (3) a positive regulation of JACKDAW by MAGPIE. The procedures proposed here greatly reduce the number of possible Boolean functions that are biologically meaningful and experimentally testable and that do not contradict previous data. We believe that these procedures can be used on any Boolean network. However, because the procedures were designed for the specific case of the RSCN, formal demonstrations of the procedures should be shown in future efforts.

Highlights

The Arabidopsis thaliana root stem cell niche (RSCN) consists of a group of cells that rarely divide, known as the quiescent center, surrounded by four different types of stem cells (Figure 1; Dolan et al, 1993)
The second mechanism involves the transcription factors SHORTROOT (SHR), SCARECROW (SCR), and some of their target genes (TGEN), as well as proteins that interact with them (Sabatini et al, 2003; Welch et al, 2007)
METHODS we describe the update to the RSCN gene regulatory network (GRN) and the procedures used to reduce the number of possible Boolean function (BF) generated when trying to predict missing interactions and maintain previous experimental data

Summary

Introduction

The Arabidopsis thaliana root stem cell niche (RSCN) consists of a group of cells that rarely divide, known as the quiescent center, surrounded by four different types of stem cells (Figure 1; Dolan et al, 1993). Due to its architectural simplicity and its accessibility for experimental research at the genetic and molecular levels, the A. thaliana RSCN has become an important experimental model for molecular genetic studies in the last few decades. During this time, many important molecular mechanisms involved in the maintenance and development of the RSCN have been described (Sablowski, 2011; Azpeitia and Alvarez-Buylla, 2012). The third mechanism includes CLAVATA-like 40 (CLE40) and WUSCHEL-RELATED HOMEOBOX 5 (WOX5; Stahl et al, 2009) These three mechanisms are interconnected and present complex non-linear behaviors (reviewed in Azpeitia and Alvarez-Buylla, 2012)

Objectives

Methods

Conclusion