A bistable circuit involving SCARECROW-RETINOBLASTOMA integrates cues to inform asymmetric stem cell division

Alfredo Cruz-Ramírez, Sara Díaz-Triviño, Ikram Blilou, Verônica A. Grieneisen, Rosangela Sozzani, Christos Zamioudis, Pál Miskolczi, Jeroen Nieuwland, René Benjamins, Pankaj Dhonukshe, Juan Caballero-Pérez, Beatrix Horvath, Yuchen Long, Ari Pekka Mähönen, Hongtao Zhang, Jian Xu, James A.H. Murray, Philip N. Benfey, Laszlo Bako, Athanasius F.M. Marée*Ben Scheres

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

233 Scopus citations


In plants, where cells cannot migrate, asymmetric cell divisions (ACDs) must be confined to the appropriate spatial context. We investigate tissue-generating asymmetric divisions in a stem cell daughter within the Arabidopsis root. Spatial restriction of these divisions requires physical binding of the stem cell regulator SCARECROW (SCR) by the RETINOBLASTOMA-RELATED (RBR) protein. In the stem cell niche, SCR activity is counteracted by phosphorylation of RBR through a cyclinD6;1-CDK complex. This cyclin is itself under transcriptional control of SCR and its partner SHORT ROOT (SHR), creating a robust bistable circuit with either high or low SHR-SCR complex activity. Auxin biases this circuit by promoting CYCD6;1 transcription. Mathematical modeling shows that ACDs are only switched on after integration of radial and longitudinal information, determined by SHR and auxin distribution, respectively. Coupling of cell-cycle progression to protein degradation resets the circuit, resulting in a "flip flop" that constrains asymmetric cell division to the stem cell region.

Original languageEnglish (US)
Pages (from-to)1002-1015
Number of pages14
Issue number5
StatePublished - Aug 31 2012
Externally publishedYes

Bibliographical note

Funding Information:
We thank Dominique Bergmann for critically reviewing this manuscript; Fred Sack, Lieven de Veylder, Naohiro Kato, Dorus Gadella, Joachim Goedhart, Tom Beeckman, and Tom Bennett for materials; and Anahí Pérez-Torres, Luis Herrera-Estrella, and Juan Carlos del Pozo for technical advice. B.S. was supported by an ERC Advanced Investigator Fellowship and by ALW-ERAPG grant 855.50.017. A.C.-R. was supported by EMBO-ALTF 1114-2006 and CONACYT 000000000092916 grants. S.D.-T. was funded by Ministerio de Educacion y Ciencia, Spain, and by Marie Curie IEF (IEF-2008-237643). V.A.G. was supported by the Dorothy Hodgkin Fellowship. V.A.G. and A.F.M.M. were supported by the UK Biological and Biotechnology Research Council (BBSRC) via grant BB/J004553/1 to the John Innes Centre. I.B. was sponsored by an NWO VIDI grant. P.N.B. was funded by NIH grant R01-GM043778. L.B. was supported by Swedish Research Council and by Carl Tryggers Stiftelse grants. Work in James A.H. Murray laboratory was supported by the BBSRC grant BB/G00482X and by the ERASysBio+ initiative under the EU FP7 ERA-NET Plus scheme.

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'A bistable circuit involving SCARECROW-RETINOBLASTOMA integrates cues to inform asymmetric stem cell division'. Together they form a unique fingerprint.

Cite this