TY - JOUR
T1 - A bistable circuit involving SCARECROW-RETINOBLASTOMA integrates cues to inform asymmetric stem cell division
AU - Cruz-Ramírez, Alfredo
AU - Díaz-Triviño, Sara
AU - Blilou, Ikram
AU - Grieneisen, Verônica A.
AU - Sozzani, Rosangela
AU - Zamioudis, Christos
AU - Miskolczi, Pál
AU - Nieuwland, Jeroen
AU - Benjamins, René
AU - Dhonukshe, Pankaj
AU - Caballero-Pérez, Juan
AU - Horvath, Beatrix
AU - Long, Yuchen
AU - Mähönen, Ari Pekka
AU - Zhang, Hongtao
AU - Xu, Jian
AU - Murray, James A.H.
AU - Benfey, Philip N.
AU - Bako, Laszlo
AU - Marée, Athanasius F.M.
AU - Scheres, Ben
N1 - 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.
PY - 2012/8/31
Y1 - 2012/8/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84865694816&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2012.07.017
DO - 10.1016/j.cell.2012.07.017
M3 - Article
C2 - 22921914
AN - SCOPUS:84865694816
SN - 0092-8674
VL - 150
SP - 1002
EP - 1015
JO - Cell
JF - Cell
IS - 5
ER -