Fucci!

We develop and apply a family of genetically encoded cell cycle biosensors based on the Fucci platform developed by Prof. Atsushi Miyawaki and Dr Asako Sakaue-Sawano (RIKEN). Our biosensors enable real-time visualisation of cell cycle dynamics in live cells, tissues and whole organisms.

Our biosensor family

We have developed five biosensor variants, each optimised for different experimental contexts:

Fucci biosensor variants

Fucci(SA) — the original Fucci2a bicistronic biosensor, marking G1 in red and S/G2/M in green (Mort et al. Cell Cycle 2014)
H2B-Fucci(SA) — tricistronic version incorporating H2B-Cerulean for precise single-cell tracking (Loftus et al. Dev Cell 2025)
Fucci(CA) — the latest Fucci(CA) variant as a bicistronic construct marking G1, S, G2/M (Sakaue-Sawano et al. Mol Cell 2017)
H1.0-Fucci(CA) — tricistronic version of Fucci(CA) incorporating H1.0-Cerulean for improved single cell tracking (Sudderick et al. bioRxiv 2026)
Qucci — our new extended tricistronic cell cycle biosensor incorporating a p27k−Cerulean reporter to mark quiescent G0 cells alongside cycling populations

How they work

Fucci biosensors exploit the oscillating abundance of cell cycle-regulated proteins to mark distinct phases with spectrally separable fluorescent reporters.

Fucci(SA)

The original Fucci(SA) probe pair comprises a fusion of monomeric Kusabira Orange (mKO2 – red) with a truncated human CDT1 (amino acids 30–120), and a fusion of monomeric Azami Green (mAG – green) with the N-terminal 110 amino acids of human Geminin (GMNN). The red probe accumulates in G1 phase, labelling nuclei red, and is degraded at the G1–S transition via SCF^Skp2. The green probe accumulates during S, G2 and M phases, labelling nuclei green, and is rapidly degraded before cytokinesis via APC/C.

An improved version of Fucci(SA) – replaces mKO2 and mAG with mCherry and mVenus respectively, increasing signal separation and compatibility with other reporters. Incorporation of a 2A self-cleaving peptide enabled equimolar co-expression of both reporters from a single promoter (Fucci2a or tandem-Fucci(SA)), facilitating the development of Cre-inducible mouse models.

Fucci(CA)

The tandem-Fucci(CA) probe pair updates the CDT1 probe from Fucci(SA) by removing the SCF^Skp2-targeted Cy motif and instead incorporating an N-terminal PIP box, which targets CDT1 for degradation in S-phase via CUL4^Ddb1. This results in CDT1 accumulation from the S–G2 transition through G2, M and G1, with rapid degradation at the G1/S boundary. With just two sensors, Fucci(CA) labels G1-phase nuclei red, S-phase nuclei green, and G2/M nuclei yellow.

Mouse lines

The R26Fucci2aR, R26Fucci2a, R26Arl13b-Fucci2aR and R26Arl13b-Fucci2a mice were generated by knocking Cre-inducible Fucci2a biosensors into the ROSA26 locus by homologous recombination (Mort et al. 2014, Ford et al. 2018). They allow ubiquitous or Cre-activated expression of the biosensor and are freely available from:

For further details and access instructions please see our Resources page.

Impact

Our mouse lines and biosensor platform have been adopted by over 54 research groups worldwide, spanning 12 biological fields including stem cell biology, cancer, neuroscience, developmental biology and immunology. The interactive network below maps citations and adoptions of our three key papers.

Interactive citation network coming soon — click image to enlarge

Key publications

Fucci2a: a bicistronic cell cycle reporter that allows Cre mediated tissue specific expression in mice. Mort RL, Ford MJ, Sakaue-Sawano A, Lindstrom NO, Casadio A, Douglas AT, Keighren MA, Hohenstein P, Miyawaki A, Jackson IJ. Cell Cycle. 2014;13(17):2681-96.

A Cell/Cilia Cycle Biosensor for Single-Cell Kinetics Reveals Persistence of Cilia after G1/S Transition Is a General Property in Cells and Mice. Ford MJ, Yeyati PL, Mali GR, Keighren MA, Waddell SH, Mjoseng HK, Douglas AT, Hall EA, Sakaue-Sawano A, Miyawaki A, Meehan RR, Boulter L, Jackson IJ, Mill P, Mort RL. Developmental Cell. 2018;47(4):509-523.

Genetically Encoded Tools for Optical Dissection of the Mammalian Cell Cycle. Sakaue-Sawano A, Yo M, Komatsu N, Hiratsuka T, Kogure T, Hoshida T, Ishidate Y, Toda S, Matsuda H, Miyawaki A. Molecular Cell. 2017;68(3):626-640.

An ILK/STAT3 pathway controls glioblastoma stem cell plasticity. Loftus AEP, Romano MS, Phuong AN, McKinnel BJ, Muir MT, Furqan M, Dawson JC, Avalle L, Douglas AT, Mort RL, Byron A, Carragher NO, Pollard SM, Brunton VG, Frame MC. Developmental Cell. 2024;59(24):3197-3212.

FuChi: A cell cycle biosensor expressing chicken for live imaging of cell cycle kinetics during avian development. Sudderick ZR, Briggs T, Van Kerckvoorde M et al. bioRxiv (in revision at PLoS Biology).

Collaborative publications

The following publications arose from active collaborations in which the Fucci2a platform was used alongside direct scientific contributions from the Mort Lab.

Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration. Aloia L, McKie MA, Vernaz G, Cordero-Espinoza L, Aleksieva N, van den Ameele J, Antonica F, Font-Cunill B, Raven A, Cigliano RA, Belenguer G, Mort RL, Brand AH, Zernicka-Goetz M, Forbes SJ, Miska EA, Huch M. Nature Cell Biology. 2019;21(11):1321-1333.

Defining the Identity and Dynamics of Adult Gastric Isthmus Stem Cells. Han S, Fink J, Jörg DJ, Lee E, Yum MK, Chatzeli L, Merker SR, Josserand M, Trendafilova T, Andersson-Rolf A, Dabrowska C, Kim H, Naumann R, Lee JH, Sasaki N, Mort RL, Basak O, Clevers H, Stange DE, Philpott A, Kim JK, Simons BD, Koo BK. Cell Stem Cell. 2019;25(3):342-356.

Concerted cell divisions in embryonic visceral endoderm guide anterior visceral endoderm migration. Antonica F, Orietti LC, Mort RL, Zernicka-Goetz M. Developmental Biology. 2019;450(2):132-140.