Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A group of receptor kinases are essential for CLAVATA signalling to maintain stem cell homeostasis


Continuous organ initiation and outgrowth in plants relies on the proliferation and differentiation of stem cells maintained by the CLAVATA (CLV)–WUSCHEL (WUS) negative-feedback loop1,2,3. Leucine-rich repeat receptor-like protein kinases (LRR-RLKs), including CLV1, BARELY ANY MERISTEMS and RECEPTOR-LIKE PROTEIN KINASE 2 (RPK2), a receptor-like protein CLV2 and a pseudokinase CORYNE (CRN) are involved in the perception of the CLV3 signal to repress WUS expression4,5,6,7,8,9,10. WUS, a homeodomain transcription factor, in turn directly activates CLV3 expression and promotes stem cell activity in the shoot apical meristem11,12. However, the signalling mechanism immediately following the perception of CLV3 by its receptors is poorly understood. Here, we show that a group of LRR-RLKs, designated as CLAVATA3 INSENSITIVE RECEPTOR KINASES (CIKs), have essential roles in regulating CLV3-mediated stem cell homeostasis. The cik1234 quadruple mutant exhibits a significantly enlarged SAM, resembling clv mutants. Genetic analyses and biochemical assays demonstrated that CIKs function as co-receptors of CLV1, CLV2/CRN and RPK2 to mediate CLV3 signalling through phosphorylation. Our findings not only widen the understanding of the underlying mechanism of CLV3 signal transduction in regulating stem cell fate but also reveal a novel group of RLKs that function as co-receptors to possibly mediate multiple extrinsic and intrinsic signals during plant growth and development.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: CIKs are essential for maintaining the shoot stem cell homeostasis.
Fig. 2: CIKs are involved in the CLV3-mediated signalling pathway.
Fig. 3: CIKs integrate all three parallel receptor kinase-mediated pathways to transduce the CLV3 signal.
Fig. 4: CIKs function as co-receptors of CLV1, CRN and RPK2.


  1. 1.

    Fletcher, J. C., Brand, U., Running, M. P., Simon, R. & Meyerowitz, E. M. Signaling of cell fate decisions by CLAVATA3 in Arabidopsis shoot meristems. Science 283, 1911–1914 (1999).

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Brand, U., Fletcher, J. C., Hobe, M., Meyerowitz, E. M. & Simon, R. Dependence of stem cell fate in Arabidopsis on a feedback loop regulated by CLV3 activity. Science 289, 617–619 (2000).

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Schoof, H. et al. The stem cell population of Arabidopsis shoot meristems is maintained by a regulatory loop between the CLAVATA and WUSCHEL genes. Cell 100, 635–644 (2000).

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Clark, S. E., Williams, R. W. & Meyerowitz, E. M. The CLAVATA1 gene encodes a putative receptor kinase that controls shoot and floral meristem size in Arabidopsis. Cell 89, 575–585 (1997).

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Ogawa, M., Shinohara, H., Sakagami, Y. & Matsubayashi, Y. Arabidopsis CLV3 peptide directly binds CLV1 ectodomain. Science 319, 294 (2008).

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Nimchuk, Z. L., Zhou, Y., Tarr, P. T., Peterson, B. A. & Meyerowitz, E. M. Plant stem cell maintenance by transcriptional cross-regulation of related receptor kinases. Development 142, 1043–1049 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Shinohara, H. & Matsubayashi, Y. Reevaluation of the CLV3-receptor interaction in the shoot apical meristem: dissection of the CLV3 signaling pathway from a direct ligand-binding point of view. Plant J. 82, 328–336 (2015).

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Kinoshita, A. et al. RPK2 is an essential receptor-like kinase that transmits the CLV3 signal in Arabidopsis. Development 137, 3911–3920 (2010).

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Kayes, J. M. & Clark, S. E. CLAVATA2, a regulator of meristem and organ development in Arabidopsis. Development 125, 3843–3851 (1998).

    CAS  PubMed  Google Scholar 

  10. 10.

    Müller, R., Bleckmann, A. & Simon, R. The receptor kinase CORYNE of Arabidopsis transmits the stem cell-limiting signal CLAVATA3 independently of CLAVATA1. Plant Cell 20, 934–946 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Mayer, K. F. et al. Role of WUSCHEL in regulating stem cell fate in the Arabidopsis shoot meristem. Cell 95, 805–815 (1998).

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Yadav, R. K. et al. WUSCHEL protein movement mediates stem cell homeostasis in the Arabidopsis shoot apex. Genes Dev. 25, 2025–2030 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Gou, X. et al. Genome-wide cloning and sequence analysis of leucine-rich repeat receptor-like protein kinase genes in Arabidopsis thaliana. BMC Genomics 11, 19 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Li, J. & Chory, J. A putative leucine-rich repeat receptor kinase involved in brassinosteroid signal transduction. Cell 90, 929–938 (1997).

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Li, J. et al. BAK1, an Arabidopsis LRR receptor-like protein kinase, interacts with BRI1 and modulates brassinosteroid signaling. Cell 110, 213–222 (2002).

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Santiago, J., Henzler, C. & Hothorn, M. Molecular mechanism for plant steroid receptor activation by somatic embryogenesis co-receptor kinases. Science 341, 889–892 (2013).

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Gómez-Gómez, L. & Boller, T. FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis. Mol. Cell 5, 1003–1011 (2000).

    Article  PubMed  Google Scholar 

  18. 18.

    Chinchilla, D. et al. A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence. Nature 448, 497–500 (2007).

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Sun, Y. et al. Structural basis for flg22-induced activation of the Arabidopsis FLS2–BAK1 immune complex. Science 342, 624–628 (2013).

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Matsubayashi, Y., Ogawa, M., Morita, A. & Sakagami, Y. An LRR receptor kinase involved in perception of a peptide plant hormone, phytosulfokine. Science 296, 1470–1472 (2002).

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Wang, J. et al. Allosteric receptor activation by the plant peptide hormone phytosulfokine. Nature 525, 265–268 (2015).

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Ishida, T. et al. Heterotrimeric G proteins control stem cell proliferation through CLAVATA signaling in Arabidopsis. EMBO Rep. 15, 1202–1209 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Ito, Y. et al. Dodeca-CLE peptides as suppressors of plant stem cell differentiation. Science 313, 842–845 (2006).

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Fontes, E. P., Santos, A. A., Luz, D. F., Waclawovsky, A. J. & Chory, J. The geminivirus nuclear shuttle protein is a virulence factor that suppresses transmembrane receptor kinase activity. Genes Dev. 18, 2545–2556 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Xu, F. et al. A soybean dual-specificity kinase, GmSARK, and its Arabidopsis homolog, AtSARK, regulate leaf senescence through synergistic actions of auxin and ethylene. Plant Physiol. 157, 2131–2153 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Suzaki, T. et al. The gene FLORAL ORGAN NUMBER1 regulates floral meristem size in rice and encodes a leucine-rich repeat receptor kinase orthologous to Arabidopsis CLAVATA1. Development 131, 5649–5657 (2004).

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Bommert, P. et al. thick tasseldwarf1 encodes a putative maize ortholog of the Arabidopsis CLAVATA1 leucine-rich repeat receptor-like kinase. Development 132, 1235–1245 (2005).

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Xu, C. et al. A cascade of arabinosyltransferases controls shoot meristem size in tomato. Nat. Genet. 47, 784–792 (2015).

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Gou, X. et al. Genetic evidence for an indispensable role of somatic embryogenesis receptor kinases in brassinosteroid signaling. PLoS Genet. 8, e1002452 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Obrdlik, P. et al. K+ channel interactions detected by a genetic system optimized for systematic studies of membrane protein interactions. Proc. Natl Acad. Sci. USA 101, 12242–12247 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Lu, Q. et al. Arabidopsis homolog of the yeast TREX-2 mRNA export complex: components and anchoring nucleoporin. Plant J. 61, 259–270 (2010).

    CAS  Article  PubMed  Google Scholar 

Download references


We are grateful to the Arabidopsis Biological Resource Center (ABRC) and the Nottingham Arabidopsis Stock Centre (NASC) for providing the T-DNA insertion lines used in this study. We thank H. Li (Core Facility for Life Science Research, Lanzhou University) for SEM technique assistance, and D. Braun (University of Missouri) for his critical reading of the manuscript. This work was supported by the National Natural Science Foundation of China (31770312, 31471402, 31270229 and 31070283), the Ministry of Education (113058A and NCET-12-0249), the 111 Project (B16022), the Fundamental Research Funds for the Central Universities (lzujbky-2017-it01, lzujbky-2017-kb05 and 2022013zrk014) and the Gansu Provincial Science & Technology Department (17ZD2NA015-06 and 17ZD2NA016-5).

Author information




C.H. and X.G. designed all experiments, analysed the data and wrote the manuscript. C.H. performed most of the experiments and prepared the data. Y.Z. conducted the pull-down, in vitro phosphorylation assays and physiological treatment of CLEs on roots. Y.C. performed the RNA in situ hybridization analyses. K.C. contributed to the high-order mutants. W.L. contributed to the maize experiments. M.Z., H.Y., Z.W., L.Z. and Y.X. contributed to the generation and analysis of myriad transgenic plants. Y.Z., Z.W., M.L., J.Y., S.H., K.H. and J.L. helped prepare the manuscript.

Corresponding author

Correspondence to Xiaoping Gou.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Figures 1–11 and Supplementary Table 1.

Life Sciences Reporting Summary

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hu, C., Zhu, Y., Cui, Y. et al. A group of receptor kinases are essential for CLAVATA signalling to maintain stem cell homeostasis. Nature Plants 4, 205–211 (2018).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing