The development of an adult organism from a fertilized egg remains one of the deep mysteries of biology. Great strides have been made in the past three decades, primarily through ever more sophisticated genetic analyses and the advent of live-cell imaging, yet the underlying principles governing development are elusive. Recently, a new generation of biological physicists has entered the field, attracted by the hallmarks of development— coordinated dynamics and pattern formation arising from cell-cell interactions—which reflect tantalizing analogs with many-body systems in condensed matter physics and related fields. There have been corresponding influxes of researchers from other quantitative disciplines. With new workers come new questions and foci at different scales in space, time and complexity. The reductionist philosophy of developmental genetics has become increasingly complemented by a search for effective mechanisms at higher scales, a strategy which has a proven track record of success in the study of complex systems in physics. Are there new and universal mechanisms of development, supra-genetic in nature, waiting to be discovered by focusing on higher scales, or is development fundamentally the intricately scripted unfolding of complex genetic instructions?
In this special focus issue of Physical Biology, we present cutting-edge research into embryo development from a broad spectrum of groups representing cell and developmental biology, biological physics, bioengineering and biomathematics. We are provided with a sense of how this multidisciplinary community views the fundamental issue of scale in development and are given some excellent examples of how we can bridge these scales through interdisciplinary collaboration, in order to create new levels of understanding.
We start with two reviews which will provide newcomers with a guide to some of the outstanding questions in the field. Winklbauer and Müller use the phenomenon of mesoderm spreading as a platform to discuss the fascinating challenge of connecting cell-level behaviours to tissue-scale dynamics, thereby putting meat on the bones of traditional physical metaphors of 'the embryonic tissue as a material'. A fresh look at natural variation in embryonic phenotypes through the lens of physics, especially mechanics, is provided by von Dassow and Davidson. They stress the importance of environmental scales in providing both physical challenges and an evolutionary backdrop for robust development. The next two papers are concerned with the crucial role of signalling in morphogenesis. Zartman et al study in detail a stage of oogenesis in Drosophila, and show how quantitative experimental determination of pattern formation can be used as a stringent test of proposed underlying molecular mechanisms; in turn, they show how such selected mechanisms can thereafter be tested by newly designed experiments. Streichan et al consider collective cell motion in the zebrafish embryo. They propose an elegant theoretical mechanism to explain how directed collective cell motion can be generated in a uniform signalling landscape through a non-linear chemotactic feedback loop, and propose experimental tests of this idea. The next two papers describe state-of-the-art spatio-temporal quantification of whole embryo dynamics with cell-level resolution. Fernandez-Gonzalez and Zallen study the fascinating phenomenon of cell surface oscillations during axis elongation in Drosophila. They use a newly designed computer algorithm to measure spatio-temporal statistics of the oscillations and connect this information to intracellular actomyosin dynamics. Szabó et al study extracellular matrix (ECM) dynamics during primitive streak extension in the avian embryo. Using computer tracking and analysis they are able to measure spatial and temporal correlations of the ECM during development and use this data to inform the crucial, yet poorly understood, role of cell-ECM interactions. The last two papers are companion articles by Sandersius et al. The first paper describes the integration of active subcellular dynamics into an existing multicellular simulation algorithm. The resulting algorithm, which is parameterized at length and time scales of microns and seconds, is capable of reproducing various experimentally observed phenotypes at significantly higher scales, namely large-strain cell stretching, effective viscosity of embryonic epithelia and streaming patterns of collective cell motion within tissues. The second paper uses this new algorithm to quantitatively test the hypothesis that a dipolar arrangement of chemotactic sources is capable of driving primitive streak formation in amniotes. The hypothesis is found to be consistent with experimental data on cell movement patterns and quantitative estimates are given for the robustness of the chemotaxis mechanism.
Is the simplest model of an embryo an embryo? Alternatively, are there higher scales of understanding that will provide predictive and powerful new insights into development? We hope this special focus issue of Physical Biology will provide a snapshot of how quantitative and interdisciplinary approaches are helping to answer these fundamental questions.