“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. Flexible Frogs (Natural variation in embryo mechanics: gastrulation in Xenopus laevis is highly robust to variation in tissue stiffness, by Michelangelo von Dassow, Lance A. Davidson, Dev Dyn 238:2–18) This study opens up a discussion rarely heard in developmental biology circles, how does tissue stiffness contribute to morphogenesis? To address this question, the authors used a microaspirator, placing a gastrulating Xenopus embryo against a channel that bridged low and high pressure reservoir. Apparent stiffness was gauged by measuring the amount of tissue displacement upon application of suction at a specified pressure. This approach revealed that tissue rigidity is surprisingly variable. From the onset of gastrulation to blastopore closure, there was an increase of apparent stiffness. What's more, when comparing embryo-to-embryo or clutch-to-clutch, tissue stiffness varied as much as twofold. Variability is likely innate, and not a product of environment, because changes in pH and salt concentration of surrounding embryonic medium had no affect on stiffness. These data lead the authors to conclude that their fellow morphogenesis researchers should be more flexible—mechanisms that allow normal development to proceed in the face of variable tissue rigidity are arguably just as important as changes in cell shape and cell movement. Size Matters (Many ribosomal protein mutations are associated with growth impairment and tumor predisposition in zebrafish, by Kevin Lai, Adam Amsterdam, Sarah Farrington, Roderick T. Bronson, Nancy Hopkins, Jacqueline A. Lees, Dev Dyn 238:76–85) It is often the little things which matter most. Here, the authors follow up on their previous finding that heterozygous zebrafish lines with retroviral insertions in ribosomal protein (rp) genes are susceptible to developing tumors. They report that 60% of 28 rp mutant lines examined are prone to acquiring malignant tumors, predominantly peripheral nerve sheath tumors which occur in only 1 in 2,000 non-rp mutant fish. Strikingly, the most tumor-prone lines are also growth impaired, but the correlation between the two is not absolute. Nevertheless, the data suggest that the same cellular defect may underlie both phenotypes. To determine the nature of the defect, donor heterozygous mutant cells were injected into wild-type hosts and vice versa. In both cases mutant cells were out-competed by wild-type cells in chimeric fish, as determined by real time polymerase chain reaction, suggesting the defect manifests itself at the cellular level. Precisely what the defect is remains to be determined. The distinction between rp mutations that lead to slower growth and tumorigenesis, and those that do not, does not correlate with the level of knockdown of a given rp gene. Also translation is not globally impaired in slow growing mutants since the proportion of ribosomes bound in monosomes or polysomes in rp heterozygotes appears the same as in wild-types. It will be important to determine what these little fish are telling us about mechanisms of tumorigenesis. Expect the Unexpected (Muscle degeneration and leukocyte infiltration caused by mutation of zebrafish fad24, by Kevin B. Walters, M. Ernest Dodd, Jonathan R. Mathias, Andrea J. Gallagher, David A. Bennin, Jennifer Rhodes, John P. Kanki, A. Thomas Look, Yevgenya Grinblat, Anna Huttenlocher, Dev Dyn 238:86–99). Leave it to a screen to yield unexpected answers to the question asked. In search of genes that regulate inflammation, Huttenlocher's screen identified zebrafish with increased neutrophil distribution in the trunk. The cause was unanticipated—a near or total loss of function of factor for adipocyte differentiation 24 (fad24), a gene they show regulates lipid metabolism like its human counterpart. In addition to decreased lipid concentrations in multiple tissues, embryos also had small eyes, heart folding defects, disorganized skeletal muscle, and other developmental abnormalities. These phenotypes are similar to those found in embryos that are nutritionally deprived, and those in which yolk lipids fail to be transported throughout the body. Further characterizing the inflammation phenotype, they found that skeletal muscle, which continued to degenerate over time, was populated by neutrophils. Application of pan-caspase inhibitors reduced observed apoptosis in skeletal muscle, as well as neutrophil infiltration. These data are evidence that apoptosis is involved in recruiting neutrophils to the trunk—a revealing finding because signals that regulate neutrophil recruitment are largely unknown. The screen has thrust the authors into relatively unexplored territory: mechanisms that connect lipid metabolism to muscle degeneration and neutrophil infiltration.
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May 24, 2021
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Open Access