Editorial overview: Taking measure of developing plants and animals

The plant or animal body develops from a single cell by growth in cell number and by the emergence of pattern. It is a beautiful thing to observe and comprehend. The developing body is a dynamical system driven by the actions of biochemistry, symmetry-breaking, self-organization, and high dimensional states represented by the vast number of cells differentiating over time and space.

The past 70 years have seen great advances in our knowledge about how model plant and animal species develop, and what genes are important for their development. We have a good qualitative picture of where cells move and how they interact with one another. However, new quantitative approaches are being applied to study of development, thanks to technical breakthroughs in microscopy, genomics, and computation. This special issue is focused on a series of reviews that provide quantitative perspectives on major problems in development.

Many of the new advances are being made thanks to importing ideas and methods from physics and mathematics. Developmental biology has long benefited from such cross-fertilization. D’Arcy Thompson was a biologist and mathematician who published the influential first edition of On Growth and Form over 100 years ago [1]. Thompson’s book is said to have inspired Alan Turing to tackle problems in developmental biology [2], but for most developmental biologists, Thompson’s work was ignored until the recent resurgence in quantitative biology. The reason for this resurgence is that new tools allow us to measure individual cells and individual molecules within cells over time. This provides an unprecedented new grasp of developmental dynamics.

It is exciting to witness the growth of quantitative developmental biology. In addition to a growing number of individual investigators becoming involved, efforts are being made to organize centers of research that mix together, biologists, physicists, and mathematicians. Such examples include the RIKEN Center for Biosystems Dynamics Research, the Max Planck Institutes in Dresden, the IBDM in Marseilles, and the NSF-Simons Centers in the U.S. We hope that such organization and coordination will continue to expand in the coming years.

The contributing authors of this special issue are all leaders in their respective fields, and they have provided important and topical summaries that provide quantitative perspectives on diverse issues regarding plant and animal development.

Morphogenesis has been a long-time focus for quantitative biologists and physicists. At the microscopic scale, cells can be autonomous drivers of tissue morphogenesis. Kate Cavanaugh, Michael Staddon, Shiladitya Banerjee, and Margaret Gardel focus on the physics of cellular adherens junctions within epithelia. Force production along these junctions is not uniform. Junctions experience very localized actomyosin flows to the interfaces between two cells and the tricellular vertices. The functional output of this junctional heterogeneity is asymmetric contraction. Ghislain Gillard and Katja Röper consider a cell-centric view of epithelial morphogenesis. During morphogenesis, cells change their shapes in complex ways, and their review examines the myriad geometries that cells adopt, and how shape dynamics are regulated.

Morphogenesis can also be studied at the mesoscopic scale. Shigeo Hayashi and Yosuke Ogura describe advances in understanding how receptor tyrosine kinases (RTKs) are re-purposed during Drosophila development. Using the ERK pathway, RTKs regulate cell fate during early embryogenesis but then switch to controlling cell morphogenesis at later stages. ERK also controls tissue homeostasis in the late embryo. Marlis Denk-Lobnig and Adam Martin illustrate how animal epithelia undergo continuous deformations during development, in particular, folding. There are multiple mechanisms that elicit folds, and different mechanisms can give rise to similar types of folds. However, some folds are created not by a single mechanism but several acting across time and spatial scales. Aurélien Villedieu, Floris Bosveld, and Yohanns Bellaïche focus on how tissue flow sculpts a developing organism. They coin the term ‘mechanical induction’ to describe when an autonomously deforming tissue region induces tissue flow in a responding region via mechanical force transduction. This perspective goes beyond considering forces acting at the cellular scale and considering instead forces acting at the tissue and inter-tissue scales.

Vertebrates have also served as important models to study morphogenesis. Chih-Wen Chu, Geneva Masak, Jing Yang, and Lance Davidson describe efforts to explore the role of mechanical cues in guiding cilia differentiation, axonal pathfinding, goblet cell regeneration, epithelial-to-mesenchymal transitions in neural crest, and mesenchymal-to-epithelial transitions in heart progenitors. For all, the African clawed frog Xenopus has served as an excellent model. John Durel and Nandan Nerurkar discuss organogenesis of endodermal derivatives such as the intestine and lungs. Lung and intestine morphogenesis have several mechanical commonalities. For example, lung branching, intestinal looping, and villification all rely on heterogeneities in tissue stiffness and growth rates, generating forces that are accommodated through buckling.

At a systems level, a variety of developmental phenomena are being studied. Andy Oates discusses the latest advances in understanding how the vertebrate trunk mesoderm is segmented into somites. Somites emerge rhythmically and sequentially in bilateral pairs from the posterior-most mesoderm of the elongating embryo. The progenitor cells in these tissues undergo coordinated oscillations in gene expression, forming a tissue-level rhythmic system. Key dynamical issues discussed include what drives the oscillations at the cellular level, and what coordinates the oscillations between neighboring cells. Alexandria Volkening outlines our current understanding of skin pigmentation pattern formation in the zebrafish. There is a broad range of mutant patterns that form as mutant fish grow due to cell interactions that have been altered. Because zebrafish have been extensively studied in the lab, mathematicians have used this knowledge-base to build models that make experimentally testable predictions about pattern formation of the skin. Mie Wong and Darren Gilmour describe the remarkable ability of developing organisms to adapt to variable or fluctuating conditions of existence, and generate a body plan that is considerably less variable. This property, termed robustness or canalization, is built into the genetic programming of development, and the authors discuss new findings about how such mechanisms work. Finally, Mingyuan Zhu and Adrienne Roeder share their knowledge about how plants harness variability to create form. Unlike animals, which typically complete organogenesis as embryos, plants continuously create new organs throughout their lifecycles. Another striking departure from animal development is that plant organogenesis exhibits high levels of variability in cell division and differentiation. However, rather than disrupting reproducibility of plant form, the variability often contributes to, and is necessary for organ robustness. Models suggest that growth is orchestrated at larger scales to ensure proper morphogenesis.

Efforts are now being made to synthesize the body of knowledge regarding development, and create synthetic versions of multicellular life. Honesty Kim, Xiaofan Jin, David Glass, and Ingmar Riedel-Kruse review current concepts in rationally engineering and modeling spatial order and physical properties of synthetic multicellular systems. Yue Shao and Jianping Fu explain how the application of synthetic approaches are transforming our understanding of early human embryology. Different aspects of human embryo development are recreated and studied in vitro, in a controlled and quantitative manner. This has been made possible by a combination of bioengineering technologies and computational modeling applied to human embryonic stem cells.

Many of the reviews in this issue have emphasized the importance of quantitative methods for investigating development. We hope this collection of reviews will inspire current and future scientists to consider new ways for understanding how the world of plants and animals all develop from simple single-celled embryos.

Biography

Richard Carthew is a Professor of Molecular Biosciences at Northwestern University in Evanston, USA. He received his PhD from MIT. After postdoctoral training at University of California, Berkeley, he became a faculty member at University of Pittsburgh, and in 2001, moved to Northwestern. He is the Director of the NSF-Simons Center for Quantitative Biology.

Amy Shyer is an Assistant Professor and Head of the Laboratory of Morphogenesis at The Rockefeller University. Her research program focuses on how mechanical forces and molecular regulation are integrated at the multicellular level to determine morphologies in vertebrate tissues and organs.