CLV1 and CLV3: negative regulators of SAM stem cell accumulation.

Unlike most animals, higher plants continue to generate new organs post-embryonically from stem cells located within shoot, root and floral meristems. These stem cells are not permanent initials, but instead are positionally determined. Therefore, meristem maintenance depends upon a balance between stem cell division within the meristem center and differentiation toward the periphery. In the shoot apical meristem (SAM) of Arabidopsis thaliana, this balance is partly regulated by the signaling molecules CLAVATA1 (CLV1), a receptor protein kinase, and CLV3, a putative extracellular protein. Loss-of-function CLV1 and CLV3 mutants accumulate stem cells, resulting in meristem enlargement. Although genetic data suggests CLV1 and CLV3 act in the same signaling pathway, expression studies reveal that the two genes are expressed in different cell layers within the SAM. One model for their activity is that secreted CLV3 binds to the plasma membrane-associated CLV1 complex to limit stem cell accumulation either by decreasing stem cell division or increasing differentiation. Two recent papers1.xCLAVATA3, a multimeric ligand for the CLAVATA1 receptor-kinase. Trotochaud, A.E. et al. Science. 2000; 289: 613–617Crossref | PubMed | Scopus (143)See all References, 2.xDependence of stem cell fate in Arabidopsis on a feedback loop regulated by CLV3 activity. Brand, U. et al. Science. 2000; 289: 617–619Crossref | PubMed | Scopus (541)See all References support this role for CLV1 and CLV3 as a receptor and ligand pair negatively regulating SAM stem cell proliferation.Previous studies of the CLAVATA genes revealed that CLV3 is required for CLV1 activation. CLV1 can be found in an inactive 185 kDa complex or an active 450 kDa complex, but the smaller complex is seen exclusively in the absence of functional CLV3. Consistent with the receptor–ligand pair hypothesis, CLV3 can be co-immunoprecipitated only with the active CLV1 complex1xCLAVATA3, a multimeric ligand for the CLAVATA1 receptor-kinase. Trotochaud, A.E. et al. Science. 2000; 289: 613–617Crossref | PubMed | Scopus (143)See all References1. Interestingly, this interaction requires intracellular CLV1 kinase activity1xCLAVATA3, a multimeric ligand for the CLAVATA1 receptor-kinase. Trotochaud, A.E. et al. Science. 2000; 289: 613–617Crossref | PubMed | Scopus (143)See all References1. Using yeast cell lines expressing components of the CLV1 complexes, Trotochaud et al.1xCLAVATA3, a multimeric ligand for the CLAVATA1 receptor-kinase. Trotochaud, A.E. et al. Science. 2000; 289: 613–617Crossref | PubMed | Scopus (143)See all References1 demonstrate that CLV3 interacts with the CLV1 complex at the plasma membrane surface. Ligand sequestration by the receptor might be important for determining the range of activity of CLV3 and the meristem boundaries it helps to establish, because ELISA analysis revealed that 76% of CLV3 is bound by CLV1 (Ref. 1xCLAVATA3, a multimeric ligand for the CLAVATA1 receptor-kinase. Trotochaud, A.E. et al. Science. 2000; 289: 613–617Crossref | PubMed | Scopus (143)See all References1). This idea is further supported by Brand et al.2xDependence of stem cell fate in Arabidopsis on a feedback loop regulated by CLV3 activity. Brand, U. et al. Science. 2000; 289: 617–619Crossref | PubMed | Scopus (541)See all References2, who use CLV3 overexpression studies to show that stem cell proliferation is directly dependent on the amount of CLV3 activity2xDependence of stem cell fate in Arabidopsis on a feedback loop regulated by CLV3 activity. Brand, U. et al. Science. 2000; 289: 617–619Crossref | PubMed | Scopus (541)See all References2. In CaMV35S::CLV3 plants, stem cell accumulation is inversely proportional to CLV3 expression. Surprisingly, when CLV3 expression by its own promoter is raised by increasing the copy number, the meristem appears normal because CLV3 is a target of a negative feedback loop2xDependence of stem cell fate in Arabidopsis on a feedback loop regulated by CLV3 activity. Brand, U. et al. Science. 2000; 289: 617–619Crossref | PubMed | Scopus (541)See all References2. Brand et al.2xDependence of stem cell fate in Arabidopsis on a feedback loop regulated by CLV3 activity. Brand, U. et al. Science. 2000; 289: 617–619Crossref | PubMed | Scopus (541)See all References2 further show that the CLV pathway negatively regulates stem cell proliferation in part by limiting the activity of the transcription factor WUSCHEL (WUS), a gene that is important for promoting stem cell division.The CLV1 and CLV3 receptor and proteinaceous ligand pair is the first such team demonstrated within the plant kingdom. Based on these studies1.xCLAVATA3, a multimeric ligand for the CLAVATA1 receptor-kinase. Trotochaud, A.E. et al. Science. 2000; 289: 613–617Crossref | PubMed | Scopus (143)See all References, 2.xDependence of stem cell fate in Arabidopsis on a feedback loop regulated by CLV3 activity. Brand, U. et al. Science. 2000; 289: 617–619Crossref | PubMed | Scopus (541)See all References, it is clear that CLV signaling helps maintain the balance between stem cell division and differentiation by negatively regulating genes important for stem cell proliferation (e.g. WUS) while downregulating its own expression through a negative feedback loop acting on CLV3.