Zhiyong Wang

  Staff Scientist
  Department of Plant Biology
  Carnegie Institution for Science
  260 Panama Street
  Stanford, CA 94305
  Phone: (650) 739-4205
  Fax: (650) 325-6857 
  Email: zywang24@stanford.edu

Research Interests

Signaling networks and growth regulation

Each plant spends its entire lifetime, often hundreds of years, grounded in one place. To survive, plants must alter their growth and development according to both environmental condition and endogenous physiology. Thus, plant growth highly regulated by many environmental signals as well as by endogenous hormones. The goals of our research are to understand the growth regulatory systems at the molecular, cellular, and developmental levels, and to develop potential tools for improving plant productivity. To achieve these goals, we use a wide range of research approaches, including genetics, genomics, and proteomics, and we study both the model system Arabidopsis and major crops such as maize, rice, and millet. Our current research focuses on (1) how hormonal and environmental signals co-regulate gene expression and plant growth, (2) how signals are transduced and integrated through protein-protein interaction and protein posttranslational modification networks, (3) how hormones regulates cell morphogenesis and cell wall biogenesis, and (4) how hormones orchestrate stem cell maintenance and differentiation in the meristems. 

Brassinosteroid (BR) signal transduction

BR is a major growth-promoting steroid hormone that regulates a wide range of developmental and physiological processes, including seed germination, cell elongation, growth, flowering, light responses, photosynthesis, and stress tolerance. Deficiency in BR synthesis or signaling causes dramatic developmental defects, including dwarfism, male sterility, delayed flowering, reduced apical dominance, and development of light-grown morphology in the dark. In contrast, application of BR or increasing BR biosynthesis can enhance plant growth and biomass production. In maize, BR also regulates sex differentiation. Research on BR can potentially lead to means of increasing crop yield and help solve the food and energy problems of the world.
BR is perceived by the cell-surface receptor kinase BRI1 (Figure 1), which contains an extracellular leucine-rich repeat domain, similar to the Toll-like receptors in animals, and a cytoplasmic serine/threonine kinase domain. BR binds to the extracellular domain of BRI1 to activate its kinase activity. Our research demonstrated that the activated BRI1 phosphorylates the BR-signaling kinases (BSKs), BSKs phosphorylate the PP1-like phosphatase BSU1, BSU1 dephosphorylates the GSK3-like kinase BIN2, BIN2 phosphorylates transcription factors BZR1 and BZR2 (also named BES1), the protein phosphatase 2A (PP2A) dephosphorylates BZR1 and BZR2, and the phosphopeptide-binding 14-3-3 proteins bind to phosphorylated BZR1 and BZR2 to keep them in the cytoplasem. When BR level is low, BIN2 phosphorylates BZR1/BZR2 to inhibit their DNA binding activity and nuclear localization. When BR level is high, BRI1-initiated phospho-relay leads to inactivation of BIN2 and dephosphorylation/activation of BZR1 and BZR2. As DNA-binding proteins, BZR1 and BZR2 directly regulate the expression of thousands of genes, which mediate cellular and developmental responses such as cell elongation and organ boundary formation. BZR1 activates and represses different target genes by interacting with other transcription regulators, such as the co-repressor TOPLESS. Our research has thus achieved a detailed understanding of the molecular pathway of BR signal transduction.

Integration of signaling pathways in growth regulation

We have further gained insight into the molecular mechanism that integrates BR with other signaling pathways, including gibberellin (GA), auxin, light, and pathogen signals (Figure 2). Our research has uncovered a central growth regulation (CGR) module that involves direct interactions between transcription factors controlled by these signaling pathways. Specifically, BZR1 directly interacts with the phytochrome-interactor factor 4 (PIF4), the auxin response factor 6 (ARF6), and the GA-signaling DELLA proteins. These interactions mediate the synergistic interactions between BR, auxin, and GA pathways, and the antagonistic interactions between BR and light in regulating shoot growth. Downstream of, but highly integrated with, the BZR1-ARF-PIF/DELLA module, a circuit of bHLH/HLH transcription factor module provides negative feedback and positive feed-forward regulations, as well as integration of addition regulatory pathways such as immune pathways. We have also uncovered mechanisms of signal integration between BR and a receptor kinase pathway that control the differentiation of stomata (epidermal pores for gas exchange) (Figure 3). Current research on hormone regulation of root stem cell dynamics is uncovering novel mechanisms of hormone integration that are distinct from those regulating shoot growth (Figure 4).


Genomic and Proteomic Analysis of Signaling networks

To gain a comprehensive understanding of the growth regulation networks requires combinations of genetics with genomic and proteomic approaches. Modern genomic approaches, such as expression profiling and chromatin-immunoprecipitation followed by sequencing (RNA-Seq and ChIP-Seq), are powerful in identifying all target genes of a signaling pathway and revealing relationships between signaling pathways. Using these approaches, we have identified thousands of genes directly regulated by BZR1. These BZR1 target genes represent diverse cellular and developmental functions controlled by BR signaling. The BR targets include over a hundred transcription factors as well as components of other signaling pathways, such as the light, gibberellin (GA) and auxin (IAA) pathways. Similar analyses of the transcription factors controlled by light and auxin, namely PIF4 and ARF6, have revealed extensive overlaps among their target genes, which revealed a central growth-regulation network (CGN) that integrates multiple hormonal and developmental pathways for growth regulation in plants (Figure 2).

Proteomics is a powerful approach for studying signal transduction. Using proteomics, we have successfully identified key components of the BR pathway such as BSKs, PP2A, TOPLESS, and many other proteins that we are still characterizing. We continue to use advanced proteomic approaches to study signal transduction mechanisms in the model plant Arabidopsis and crops such as rice, maize and rye. These studies are expanding the posttranslational modification networks that integrate BR signal with other signaling pathways.
Our studies using genetic, genomic, and proteomic approaches have yielded a detailed understanding of how BR signal is transduced from the cell surface receptor kinase to nuclear transcription factors and how this BR pathway integrates and crosstalks with other signaling pathways in specific developmental contexts. Our current research focuses on the mechanisms of signal integration and the evolutionary comparison of the signaling networks in different plant species. Examples of ongoing research projects include: (1) proteomic identification and functional study of proteins that interact with known BR-signaling proteins; (2) functional study of BZR1 target genes; (3) BR regulation of stem cell dynamics in the meristems; (4) crosstalk between BR signaling pathway and other receptor kinase pathways; (5) proteomic and genomic studies of other signaling pathways in Arabidopsis and the BR pathway in maize.'