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In animals and plants, stem-cell niches are local microenvironments that are tightly regulated to preserve their unique identity while communicating with adjacent cells that will give rise to specialized cell types. In the primary root of Arabidopsis thaliana, two transcription factors, BRAVO and WOX5, among others, are expressed in the stem-cell niche. Intriguingly, BRAVO, a repressor of quiescent center divisions, confines its own gene expression to the stem-cell niche, as evidenced in a bravo mutant background. Here, we propose through mathematical modeling that BRAVO confines its own expression domain to the stem-cell niche by attenuating a WOX5-dependent diffusible activator of BRAVO. This negative feedback drives WOX5 activity to be spatially restricted as well. The results show that WOX5 diffusion and sequestration by binding to BRAVO are sufficient to drive the experimentally observed confined BRAVO expression at the stem-cell niche. We propose that the attenuation of a diffusible activator can be a general mechanism acting at other stem-cell niches to spatially confine genetic activity to a small region while maintaining signaling within them and with the surrounding cells., This work was supported by the Ministerio de Ciencia e Innovación (MCIN), Agencia Estatal de Investigación (AEI) and European Regional Development Fund (Fondo Europeo de Desarrollo Regional, FEDER) program ‘Una manera de hacer Europa’ MCIN/AEI/10.13039/501100011033/FEDER (PGC2018-101896-B-I00 to M.I.); Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación and European Social Fund (Fondo Social Europeo, FSE) program ‘El FSE invierte en tu futuro’ (BES-2016-078218 to J.M.); Ministerio de Ciencia e Innovación (MCIN), Agencia Estatal de Investigación (AEI) and European Regional Development Fund (ERDF) (BIO2016-78955 to A.I.C.-D.); the European Research Council (ERC) Consolidator Grant (ERC-2015-CoG–683163 to A.I.C.-D.); Generalitat de Catalunya (M.I. and J.M. in Grup de Recerca Consolidat 2017 SGR 1061; FI-DGR 2016FI-B 00472, also funded by FSE, to N.B.); and the Ministerio de Educación, Cultura y Deporte (FPU15/02822 to I.B.-P.).

Understanding stem cell regulatory circuits is the next challenge in plant biology, as these cells are essential for tissue growth and organ regeneration in response to stress. In the Arabidopsis primary root apex, stem cell-specific transcription factors BRAVO and WOX5 co-localize in the quiescent centre (QC) cells, where they commonly repress cell division so that these cells can act as a reservoir to replenish surrounding stem cells, yet their molecular connection remains unknown. Genetic and biochemical analysis indicates that BRAVO and WOX5 form a transcription factor complex that modulates gene expression in the QC cells to preserve overall root growth and architecture. Furthermore, by using mathematical modelling we establish that BRAVO uses the WOX5/BRAVO complex to promote WOX5 activity in the stem cells. Our results unveil the importance of transcriptional regulatory circuits in plant stem cell development., A.I.C-D. is a recipient of a BIO2016-78955 grant from the Spanish Ministry of Economy and Competitiveness and a European Research Council, ERC Consolidator Grant (ERC-2015-CoG – 683163). I.B-P. is funded by the FPU15/02822 grant from the Spanish Ministry of Education, Culture and Sport; N.B. by the FI-DGR 2016FI_B 00472 grant from the AGAUR, Generalitat de Catalunya; and A.P-R. by the SEV-2015-0533 from the Severo Ochoa Programme for Centers of Excellence in R&D. M.I. and J.M. acknowledge support from the Spanish Ministry of Economy and Competitiveness and FEDER (EU) through grant FIS2015-66503-C3-3-P, from Ministerio de Ciencia, Innovación y Universidades / Agencia Estatal de Investigación / Fondo Europeo de Desarrollo Regional, Unión Europea through grant PGC2018-101896-B-I00 and from the Generalitat de Catalunya through Grup de Recerca Consolidat 2014 SGR 878 and 2017 SGR 1061. J.M. is funded by the Spanish Ministry of Education through BES-2016-078218. Y.S. and R.C.D. were funded by the Deutsche Forschungsgesellschaft (DFG) (grant STA12/12 1-1). A.I.C.-D.–A.C. collaboration was funded by the European Regional Development Funds and Marie Curie IRSES Project DEANN (PIRSES-GA-2013-612583). CRAG is funded by “Severo Ochoa Programme” from Centers of Excellence in R&D 2016-2019 (SEV-2015-485 0533).