“Highlights” calls attention to exciting advances in developmental biology that have recently been reported in Developmental Dynamics. Development is a broad field encompassing many important areas. To reflect this fact, the section spotlights significant discoveries that occur across the entire spectrum of developmental events and problems: from new experimental approaches, to novel interpretations of results, to noteworthy findings utilizing different developmental organisms.

Cells and software in harmony (Mathematical Modeling of the Capillary-like Pattern Generated by Adrenomedullin-treated Human Vascular Endothelial Cells In Vitro by Diego Guidolin, Giovanna Albertin, Elisa Sorato, Barbara Oselladore, Alessandra Mascarin, and Domenico Ribatti, Dev Dyn238:1951–1963). A good mathematical model is derived from an intimate relationship with biology. So it is with the model for assembly of vascular endothelial cells (ECs) into capillary-like structures, presented here by Guidolin and colleagues. Under specific in vitro conditions, ECs self-organize into a network of tubules, a process which is enhanced by addition of pro-angiogenic factors, like adrenomedullin (AM). To determine essential cellular behaviors for pattern formation, the authors used two integrated models. The Cellular Potts Model takes into account cellular properties of chemotaxis, adhesion, and shape remodeling, and the Partial Differential Equation accounts for diffusion properties of the likely main endogenous chemoattractant, vascular endothelial growth factor (VEGF). The model was further customized with input from cell culture measurements taken by the authors. When put to the test, the simulated pattern and parameter measurements—for example number of meshes and branch points per field—closely matched that of untreated ECs. However, the model failed to predict patterns of ECs cultured with AM, revealing that it lacked input from an important cell behavior. Hypothesizing that the missing ingredient was cell proliferation, an “extended” model was generated and called upon to estimate the percentage increase in cell number that would yield observed patterns. It predicted a 0–7% increase in untreated cells and a 13–16% increase of AM-treated cells. Remarkably, bromodeoxyuridine incorporation experiments found proliferation rates of 4% in untreated and 14% in treated cells, falling within the predicted range. These results validate the model as a useful predictor of cellular properties. Biology informs model, which predicts biology, which validates model. The relationship between cells and software comes full circle.

Mountains from (micro) molehills (Proliferation of Mouse Embryonic Stem Cell Progeny and the Spontaneous Contractile Activity of Cardiomyocytes Are Affected by Microtopography by Jesse K. Biehl, Satoshi Yamanaka, Tejal A. Desai, Kenneth R. Boheler, and Brenda Russell, Dev Dyn238:1964–1973) As a cell type with unlimited cell fate potential, an embryonic stem (ES) cell's journey down the path to differentiation can be easily altered by its surrounding environment. Cells must not only negotiate a downpour of signaling molecules, but also the physical obstacle presented here, microtopography. When a heterogenous population of mouse ES (mES) progeny were plated onto membranes dotted with evenly spaced 15-μm microprojections, an apparent difference in cell density was observed. BrdU (5-bromo-2′-deoxy-uridine) labeling revealed a two-fold decreased uptake in cells plated on textured as compared to flat slides, with the most pronounced difference seen among cells in close proximity to microprojections. Proliferation rates of heterogenous progeny plated on textured slides were rescued by treatment with agents that reduce stress fiber formation, Rho kinase inhibitor, Y-27632 or myosin light chain inhibitor, ML-7. The authors hypothesize that reduced proliferation is caused by increased tension in the third dimension generated by stress fibers. A highly purified mES-derived cardiomyocyte population also behaved aberrantly when plated on the tiny hills. These cells suffered a nearly four-fold proliferation decrease, and also demonstrated abnormally variable cluster size and beating rates. This type of information should help chip away at the obstacles facing the effective use of cardiomyocytes in regenerative medicine.

Dishevelled but not ashamed (Diversification of the Expression Patterns and Developmental Functions of the Dishevelled Gene Family during Chordate Evolution by Ryan S. Gray, Roy D. Bayly, Stephen A. Green, Seema Agarwala, Christopher J. Lowe, and John B. Wallingford, Dev Dyn238:2044–2057) Transcriptional control of Dishevelled (Dvl) genes, downstream effectors of canonical and noncanonical Wnt signaling, have not received much respect. The three family members, Dvl1, Dvl2, and Dvl3, have mainly been examined in mouse, where their broad expression patterns are often referred to as “ubiquitous.” Consequently, contributions of individual Dvl genes in tissue specific regulation of Wnt signaling have largely been overlooked. Here, Gray and colleagues delve deeply into the deuterostome lineage to test whether there is more to Dvl than meets the eye. Examination of expression of the single Dvl in the basal deuterostome Saccoglossus kowalevskii reveals varied patterns throughout development, suggesting an ancestral Dvl had dynamic, tissue specific expression. Expression of the two Dvl orthologs in chick, Dvl1 and Dvl2 were also examined, and similarly showed changing expression patterns that differed from that published in mouse. Interestingly, Xenopus expression of Dvl1, 2, and 3, largely diverge from both chick and mouse expression patterns. A notable expression difference includes Xenopus Dvl1 and Dvl2 in neural crest. There are also areas of overlap, for example all three Dvl genes in Xenopus, and mouse Dvl1, are expressed in somites. Knockdown of Xenopus Dvl genes by morpholino caused tissue- and stage-specific abnormalities consistent with Dvl3 in maintenance of muscle identity and sclerotome development, and Dvl1 and 2 regulating neural crest specification and somite segmentation, only the latter of which has also been noted in mouse. Their data support the hypothesis that Dvl genes have been co-opted to regulate evolutionarily derived developmental processes, and that the three Dvl genes should proudly share the limelight with its famed upstream regulators.