Order from disorder: random cells make reproducible organs

How do organs grow to reach the same size? Counterintuitively, randomness in cell growth is important to produce organs of uniform size and shape.

HFSP Program Grant holders Arezki Boudaoud, Chun-Biu Li, Adrienne Roeder and Richard Smith and colleagues
authored on Mon, 29 August 2016

What makes an elephant look like an elephant, or a mouse look like a mouse? How do our two arms reach less than 1% dissimilarity in length? Despite continuous progress in developmental biology, we still do not know the answers to such deceptively simple questions. In other terms, one of the most important open questions in developmental biology is how an organ “knows” to stop growing when it reaches the correct size and shape. Plants are perfectly suited to address such questions because they can produce many almost identical flowers. Previous studies determined genes that make all flowers bigger or smaller, or that make all cells bigger or smaller. However, it is still unclear how all flowers within a single plant independently stop growing at the same size and shape. This process is all the more striking because microscopic observations show that cell geometries differ between flowers, just like skin folds or hair locations differ between our two arms.

Figure 1: Random directions of growth yield flowers of the correct size and shape. Credit L. Hong, Cornell University.

An HFSP funded international team (Cornell University, Hokkaido University, Max Planck Institute, Ecole Normale Supérieure de Lyon / Université Claude Bernard Lyon 1 / CNRS / INRA) unraveled how random cell growth contributes to making organs reach the correct size and shape. The team addressed the mechanisms that make flowers reproducible in the model plant Arabidopsis (thale cress), using an interdisciplinary approach combining biology, computer science, physics, and applied mathematics. They observed living cells in flowers dividing and growing with up-to-date optical microscopy and they measured physical forces within tissues with a mechanical microscope; using advanced image and statistical analyses, they found that cell behaviour appears significantly random with neighbouring cells growing in different directions.

Figure 2: Random directions of growth yield flowers of the correct size and shape. Credit S. Tsugawa, Hokkaido University.

They then incorporated these observations into a mathematical model of tissue growth from which they deduced that reaching reproducible shapes requires that cells also change growth direction randomly in time, which can be intuitively understood as follows. Imagine a crowd in which every person aims at a random landmark and walks towards the landmark: the crowd will soon disperse. Now if every person changes landmark to another random landmark each five seconds, persons will wander around and the crowd will stay together for a longer time.

In order to test this model, the team sought a gene such that, when plants lack a functional version of this gene (which is mutated), flowers differ in size and shape within a single plant. They identified such a gene that regulates the level of oxidant chemicals species. Interestingly, increasing the levels of vitamin C (a well-known antioxidant) in normal plants makes flowers bigger. In plants lacking this gene, cell growth appears as less random than in normal plants yielding, surprisingly, more randomness in flower size.

Altogether, this work challenges the classical view that the development of an organism is a well-orchestrated chain of cellular events and shows that order can emerge from disorder in the normal functioning of a living being. This study was published in Developmental Cell on July 11th.

Reference

Variable Cell Growth Yields Reproducible Organ Development through Spatiotemporal Averaging. Hong, L.*, Dumond, M.*, Tsugawa, S.*, Sapala, A, Routier-Kierzkowska, A.-L., Zhou, Y., Chen C., Kiss, A., Zhu, M., Hamant, O., Smith, R.S., Komatsuzaki, T., Li, C.-B., Boudaoud, A^, and Roeder, A.H.K.^ (2016) Dev Cell 38:15-32. doi:10.1016/j.devcel.2016.06.016. * Co-first authors ^ Co-corresponding authors

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Developmental Cell Preview: Right Place Right Time: Heterogeneity-Driven Organ Geometry

Cornell Chronicle: Flower bud uniformity beholden to time and space