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

Research in my lab focuses on elucidating the signaling mechanisms underlying growth regulation and environmental adaptation. Plants have evolved high levels of developmental plasticity, which is crucial for growth and survival in highly variable environment. Underlying such developmental plasticity are complex cellular networks that integrate perception of environmental and endogenous signals with gene expression and cell differentiation programs. One goal of our research is to gain a comprehensive understanding of the regulatory systems, and we use a wide range of research approaches, including genetics, genomics, and proteomics to achieve this goal. We are particularly effective in analyzing protein-DNA binding, protein-protein interactions, and posttranslational modifications. We study both the model organism Arabidopsis and major crops such as rice, maize and sorghum. Our long-term goal is to develop effective strategies and tools for genetic improvement of plant productivity

The BR signaling network

BR is a major growth-promoting 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 and initiate a signaling cascade leading to regulation of gene expression in the nucleus. This signaling cascade includes the BR-signaling kinases (BSKs), the PP1-like phosphatase BSU1, the GSK3-like kinase BIN2, and protein phosphatase 2A (PP2A), the phosphopeptide-binding 14-3-3 proteins, and the homologous transcription factors BZR1 and BZR2 (also named BES1). When BR level is low, BIN2 phosphorylates BZR1/BZR2 and phospho-BZR1/BZR2 lose DNA binding activity and are retained in the cytoplasm by the 14-3-3 proteins. When BR level is high, BRI1 phosphorylates BSKs/CDG1 kinases which in turn phosphorylate BSU1. BSU1 dephosphorylates BIN2 to inhibit its kinase activity and to increase its ubiquitination mediated by the KIB1 E3 ubiquitin ligase. As such, BR induces rapid accumulation of dephosphorylated BZR1 and BZR2/BES1 in the nucleus due to dephosphorylation by PP2A. BZR1 and BZR2 directly regulate the expression of thousands of target genes. Our work, together with that of a handful other labs, have established the BR signaling pathway as the best-understood receptor-kinase signaling pathway in plants.

Figure 1)


Signal crosstalk and Integration of pathways into networks

We have further gained insight into the molecular mechanism for integration of BR with other major growth-regulation signals, including gibberellin (GA), auxin, light, temperature, pathogen signals, and nutrient signals. Using modern genomic approaches of RNA-Seq and ChIP-Seq, we have identified thousands of genes directly regulated by BZR1, the light-regulated transcription factor PIF4, and the auxin response factor 6 (ARF6). These genome-wide targets not only identify diverse cellular and developmental functions controlled by these signaling pathways, but also revealed extensive overlaps among the target genes these distinct transcription factors. We further discovered that these TFs directly interact with each other and also interact with the gibberellin (GA) signaling DELLA proteins. Our research has thus revealed a central growth-regulation (CGR) network that integrates multiple hormonal and developmental pathways for growth regulation in plants (Figure 2). The CGR network also integrates additional signals such as temperature, sugar, the circadian clock. 

Figure 2)


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.'

Figure 3)

Recent review papers

Chaiwanon J, Wang W, Zhu JY, Oh E, Wang ZY. (2016) Information Integration and Communication in Plant Growth Regulation. Cell 164(6):1257-68.
Wang W, Bai MY, Wang ZY. (2014). The brassinosteroid signaling network – a paradigm of signal integration. Curr. Opin. Plant Biol. 21:147–153 .
Wang W and Wang ZY. (2014). At the intersection of plant growth and immunity. Cell Host Microbe 15, 400–402.
Zhu JY, Sae-Seaw J, Wang ZY. (2013). Brassinosteroid signalling. Development. 140, 1615-1620.
Wang ZY, Bai MY, Oh E, Zhu JY (2012). Brassinosteroid signaling network and regulation of photomorphogenesis. Annu. Rev. Genet. 46:701-724.
Kim TW and Wang ZY. (2010) Brassinosteroid signal transduction from receptor kinases to transcription factors. Annu. Rev. Plant Biol.61, 681-704.