Lineage dynamics

Current: Gabriel Amador, Hannah Fung, Macy Vollbrecht

Collaborators: Renee Dale

Leaves are both mostly the same, and completely different, each one made of cells that divide and grow in ways that we can’t predict. Yet collectively, these individual cellular actions lead to a coordinated whole. Mathematical modeling combined with long term imaging and experimental manipulation is letting us decipher the design principles of flexible, yet robust organ growth. Return to Main Research

The cells that make up a complex organism like a frog or a human or a plant, vary in their size and shape, but cells of a certain type have a consistent size; for example red blood cells and stem cells are quite small, while fat cells and eggs are hundreds of times larger. Over the years, many cell biologists have wondered why cell size matters. A growing body of work has shown that size matters for division competence, biosynthetic capacity, metabolic flux and stem cell capacity. How cells arrive at their optimal size is a mystery.

During development, tissue stem cells balance proliferation and differentiation. In tissues whose final size is variable, such as animal guts and muscles, or plant leaves, flexibility is achieved when the proliferation/differentiation balance can be dynamically altered in response to internal or external cues. We found that stomatal stem-cells trigger the transition from asymmetric self-renewing divisions to commitment and terminal differentiation by crossing a critical cell size threshold. Through computational simulation, we showed that this cell size-mediated transition allows robust, yet flexible termination of stem cell proliferation. Genetic manipulations enabled us to validate predictions of the simulation, and to evaluate molecular mechanisms for cell size sensing, leading to the conclusion that cell size is likely sensed in the nucleus.

Our study adds fate specification to the compendium of size-regulated processes, building on previous work on C. elegans germline fate specification and showing interesting parallels with Drosophila pupal neuroblasts. Because of the accessibility of meristemoids to long-term tracking and genetic manipulation, and the timeframe under which decisions are made, the plant system provides unique opportunities to probe the mechanisms and tissue consequences of a cell-size based fate decision.

Some recent papers on this theme:

Function follows form: How cell size is harnessed for developmental decisions (2023) Hannah Fung, lead author [link to PDF]

A cell size threshold triggers commitment to stomatal fate in Arabidopsis (2022) Yang Gong, Renee Dale, Hannah Fung, Gabriel Amador, co-lead authors [link to PDF]

Single-cell resolution of lineage trajectories in the Arabidopsis stomatal lineage and developing leaf (2021) Camila Lopez-Anido, lead author [link to PDF]