AI Insight
Researchers developed FuChi, a genetically modified chicken line that uses fluorescent biosensors to track cell cycle phases in living cells and tissues. Unlike previous Fucci systems in other animals, FuChi accurately distinguishes cells in all four major cell cycle phases (G1, S, G2, and M) and enables continuous monitoring of cell division dynamics during embryonic development. Using this system, the team mapped proliferation patterns across developing chicken tissues and discovered that the transition from S phase appears to be a critical event during gastrulation when cells exit the primitive streak to form embryonic structures.
Why it matters
FuChi provides a superior research tool for studying cell division and proliferation in a vertebrate model that is more accessible and experimentally advantageous than mice for developmental studies. This technology has broad applications for investigating embryonic development, organ growth, tissue maintenance, disease progression, and immune responses in real time.
Understand the Science
by Zoe R. Sudderick, Tiernan Briggs, Shirooza Mubarak, Melinda Van Kerckvoorde, Ana R. Hernandez Rodriguez, Sudeepta K. Panda, Jon Riddell, Cameron Batho-Samblas, Lorna Taylor, Lynn McTeir, Dominique Meunier, Amy Findlay, Flossie S. Roberts, Anna Raper, Asako Sakaue-Sawano, Atsushi Miyawaki, Joe Rainger, Jeffrey J. Schoenebeck, Cornelis J. Weijer, Mike J. McGrew, Denis J. Headon, Megan G. Davey, Richard L. Mort, James D. Glover
The ability to monitor the proliferative status of live cells both in vitro and in vivo over time has revolutionised our understanding of development, growth and disease. This was first made possible by fluorescent ubiquitination-based cell cycle indicator (Fucci) technology, which distinguishes specific cell cycle phases through the reciprocal degradation of fluorescently tagged, truncated forms of human CDT1 and GMNN proteins. Fucci genetic systems have been successfully implemented in transgenic mice, zebrafish, and axolotls. To date, no viable, stably expressing Fucci line has been developed in an avian species. Although a range of continuously improving Fucci constructs have been developed in recent years, existing in vivo Fucci models remain limited because they rely on older reporter technology that fails to distinguish cells in S, G2, and M phases or to label cells in early G1. As a result, these models can be challenging to interpret and their utility for continuous cell tracking and precise analysis of cell-cycle dynamics is limited. Here, we introduce FuChi, a multicistronic Fucci-expressing chicken line incorporating a newly optimised reporter construct composed of an mCerulean-tagged histone H1.0 linker protein fused via a self-cleaving 2A peptide to the tandem Fucci(CA)2 cell cycle biosensor, with additional epitope tags included for detection in fixed tissues. We show that this system accurately discriminates and permits tracking of cells in G1, S, G2, and M phases both in vitro and in vivo, enabling faithful visualisation of cell cycle status in intact tissues and organs. Using FuChi embryos, we mapped proliferation dynamics across developing tissues, analysed cell cycle states of migrating cells, and performed live imaging of early embryos. These latter experiments revealed that transition from S phase may be a key morphogenetic event during gastrulation as mesendoderm cells egress from the primitive streak to form embryonic structures including the prechordal plate. Pairing this advanced reporter with the intrinsic experimental advantages of the chicken embryo positions FuChi as a premier in vivo system for studying cell-cycle kinetics in development, delivering clear technological improvements over current Fucci models. FuChi chickens provide a powerful new resource for studying embryonic development, organ growth, tissue homeostasis, disease processes, and infection responses.
Source: FuChi is a cell cycle biosensor for tracking cell cycle dynamics during avian development