A SOSEKI-based coordinate system interprets global polarity cues in Arabidopsis
Yoshida, Saiko ; Schuren, Alja van der; Dop, Maritza van; Galen, Luc van; Saiga, Shunsuke ; Adibi, Milad ; Möller, Barbara ; Hove, Colette A. ten; Marhavy, Peter ; Smith, Richard ; Friml, Jiri ; Weijers, Dolf - \ 2019
Nature Plants 5 (2019)2. - ISSN 2055-026X - p. 160 - 166.
Multicellular development requires coordinated cell polarization relative to body axes, and translation to oriented cell division 1–3 . In plants, it is unknown how cell polarities are connected to organismal axes and translated to division. Here, we identify Arabidopsis SOSEKI proteins that integrate apical–basal and radial organismal axes to localize to polar cell edges. Localization does not depend on tissue context, requires cell wall integrity and is defined by a transferrable, protein-specific motif. A Domain of Unknown Function in SOSEKI proteins resembles the DIX oligomerization domain in the animal Dishevelled polarity regulator. The DIX-like domain self-interacts and is required for edge localization and for influencing division orientation, together with a second domain that defines the polar membrane domain. Our work shows that SOSEKI proteins locally interpret global polarity cues and can influence cell division orientation. Furthermore, this work reveals that, despite fundamental differences, cell polarity mechanisms in plants and animals converge on a similar protein domain.
Modeling spatial pattern formation in plant development
Adibi, Milad - \ 2017
Wageningen University. Promotor(en): V. dos Santos, co-promotor(en): C. Fleck. - Wageningen : Wageningen University - ISBN 9789462956896 - 209
plant development - mathematical models - patterns - arabidopsis thaliana - vascular system - xylem - auxins - modeling - systems biology - plantenontwikkeling - wiskundige modellen - patronen - arabidopsis thaliana - vaatsysteem - xyleem - auxinen - modelleren - systeembiologie
Modern biological research is accumulating an ever-increasing amount of information on genes and their functions. It is apparent that biological functions can very rarely be attributed to a single genes, but rather arise from complex interaction within networks that comprise many genes. A fundamentally important challenge in contemporary biology is to extract mechanistic understanding about the complex behavior of genetic networks from the available data. The interactions within a genetic network are often exceedingly complex and no-linear in nature, and thus are not open to intuitive understanding. This situation has given rise to a host of mathematical and computational approaches aimed at in-depth analysis of genetic network topologies and dynamics. In particular these approaches focus on system level proprieties of these networks, not directly derivable from their constituent components. To a large extent the power of these theoretical approaches rely on meaningful reduction in complexity by utilizing justified simplifications and abstractions. The underlying principle is that in order to comprehend a mechanism, it is not necessary to take into account all the available information about the mechanism. Given this, Computational models that follow this approach focus on incorporating core components that are essential in answering a specific biological question, while simplifying/omitting the less relevant processes. A fundamental question is this regard is what simplifying concept should be employed when developing a theoretical model of a genetic network.
A successful approach to address this question is the notion of network motif analysis. This approach is based on the core idea that most genetic networks are not arbitrary nor unique, instead they can be categorized into common network dynamics and topologies that perform core functions. Analogous to components of an electric circuit (resistors, capacitor, etc.) these network motifs have distinct properties that are independent of the network that they are embedded in. Therefore analysis of genetic networks in terms of their constituent motifs can potentially be an effective mean in obtaining mechanistic understanding about them.
In this thesis the network motif approach is utilized to study two instances of pattern formation in plant tissues. The first study focuses on organization of stem cells within the shoot apical meristem of the model plant, Arabidopsis thaliana. The results demonstrate that three interconnected network motifs can account for a range of experimental observations regarding this system. Furthermore through an exhaustive exploration of the available data, candidate genes and interactions corresponding to these motifs are outlined, thus paving the way for future interdisciplinary investigations.
The second study explores the development of vasculature during arabidopsis embryogenesis. In contrast to shoot apical mersitem in mature plant, the cell number and arrangement of vasculature in highly dynamic during its embryonic development. To account for this feature, a computational framework was utilized that is capable of capturing the interplay between genes and cell growth and division. The outcome revealed that two interlocking networks motifs dynamically control both patterning and growth of the vascular tissue. The study revealed novel spatial features of a motif previously studies exclusively in non-spatial settings. Furthermore the study resulted in a compelling example of model-driven discovery, where theoretical analysis predicted a specific cellular arrangement to be crucial for the correct development of vasculature. Subsequent analysis of experimental data confirmed the existence of this cellular arrangement in the embryo.
The projects presented in this thesis exemplify successful applications of the network motif approach in studying spatial genetic network. In both cases the networks were successfully examined in terms of their constituent motifs, which subsequently lead to increased mechanistic understanding of them. Ultimately the work presented in this thesis demonstrates the effectiveness of studying genetic networks by a combination of careful examination of available biological data and a reductionist modeling approach guided by the concept of network motifs.
Theoretical approaches to understanding root vascular patterning : A consensus between recent models
Mellor, Nathan ; Adibi, Milad ; El-Showk, Sedeer ; Rybel, Bert De; King, John ; Mähönen, Ari Pekka ; Weijers, Dolf ; Bishopp, Anthony ; Etchells, Peter - \ 2017
Journal of Experimental Botany 68 (2017)1. - ISSN 0022-0957 - p. 5 - 16.
Auxin - Cytokinin - Mathematical modeling - Organ patterning - Systems biology - Vascular development
The root vascular tissues provide an excellent system for studying organ patterning, as the specification of these tissues signals a transition from radial symmetry to bisymmetric patterns. The patterning process is controlled by the combined action of hormonal signaling/transport pathways, transcription factors, and miRNA that operate through a series of non-linear pathways to drive pattern formation collectively. With the discovery of multiple components and feedback loops controlling patterning, it has become increasingly difficult to understand how these interactions act in unison to determine pattern formation in multicellular tissues. Three independent mathematical models of root vascular patterning have been formulated in the last few years, providing an excellent example of how theoretical approaches can complement experimental studies to provide new insights into complex systems. In many aspects these models support each other; however, each study also provides its own novel findings and unique viewpoints. Here we reconcile these models by identifying the commonalities and exploring the differences between them by testing how transferable findings are between models. New simulations herein support the hypothesis that an asymmetry in auxin input can direct the formation of vascular pattern. We show that the xylem axis can act as a sole source of cytokinin and specify the correct pattern, but also that broader patterns of cytokinin production are also able to pattern the root. By comparing the three modeling approaches, we gain further insight into vascular patterning and identify several key areas for experimental investigation.
Centering the organizing center in the Arabidopsis thaliana shoot apical meristem by a combination of cytokinin signaling and self-organization
Adibi, Milad ; Yoshida, Saiko ; Weijers, Dolf ; Fleck, Christian - \ 2016
PLoS ONE 11 (2016)2. - ISSN 1932-6203
Plants have the ability to continously generate new organs by maintaining populations of stem cells throught their lives. The shoot apical meristem (SAM) provides a stable environment for the maintenance of stem cells. All cells inside the SAM divide, yet boundaries and patterns are maintained. Experimental evidence indicates that patterning is independent of cell lineage, thus a dynamic self-regulatory mechanism is required. A pivotal role in the organization of the SAM is played by the WUSCHEL gene (WUS). An important question in this regard is that how WUS expression is positioned in the SAM via a cell-lineage independent signaling mechanism. In this study we demonstrate via mathematical modeling that a combination of an inhibitor of the Cytokinin (CK) receptor, Arabidopsis histidine kinase 4 (AHK4) and two morphogens originating from the top cell layer, can plausibly account for the cell lineageindependent centering of WUS expression within SAM. Furthermore, our laser ablation and microsurgical experiments support the hypothesis that patterning in SAM occurs at the level of CK reception and signaling. The model suggests that the interplay between CK signaling, WUS/CLV feedback loop and boundary signals can account for positioning of the WUS expression, and provides directions for further experimental investigation.
Integration of growth and patterning during vascular tissue formation in Arabidopsis
Rybel, B. De; Adibi, M. ; Breda, A.S. ; Wendrich, J.R. ; Smit, M.E. ; Novák, O. ; Yamaguchi, N. ; Yoshida, S. ; Isterdael, G. van; Palovaara, J. ; Nijsse, B. ; Boekschoten, M.V. ; Hooiveld, G.J.E.J. ; Beeckman, T. ; Wagner, D. ; Ljung, K. ; Fleck, C. ; Weijers, D. - \ 2014
Science 345 (2014)6197. - ISSN 0036-8075 - 9 p.
dependent auxin gradients - solid-phase extraction - shoot apical meristem - transcription factor - root - cytokinins - purification - expression - transport - genes
Coordination of cell division and pattern formation is central to tissue and organ development, particularly in plants where walls prevent cell migration. Auxin and cytokinin are both critical for division and patterning, but it is unknown how these hormones converge upon tissue development. We identify a genetic network that reinforces an early embryonic bias in auxin distribution to create a local, nonresponding cytokinin source within the root vascular tissue. Experimental and theoretical evidence shows that these cells act as a tissue organizer by positioning the domain of oriented cell divisions. We further demonstrate that the auxin-cytokinin interaction acts as a spatial incoherent feed-forward loop, which is essential to generate distinct hormonal response zones, thus establishing a stable pattern within a growing vascular tissue.