Use of Zebrafish Embryos for Small Molecule Screening Related to CancerTerriente, Javier; Pujades, Cristina
doi: 10.1002/dvdy.23912pmid: 23203901
The introduction of mechanism‐based targeted therapies to treat human cancers is fruit of decades of research into the molecular basis of cancer pathogenesis. Despite the growing knowledge about the molecular mechanisms governing its causes and progression, there is a lack of effective treatments for many types of cancer. The expensive and time‐consuming preclinical pipeline for testing molecules slows the discovery of new therapies. Therefore, it is important to consider alternative methodologies both for accelerating therapeutic discovery and reducing costs. In that regard, zebrafish is becoming an attractive model for fast and efficient drug screening. Its use has expanded to many disease research areas, and the postgenomic era has led to the progression of functional studies and boosted the development of general databases, such as ZFIN, and the emergence of more specialized ones, including several catalogues of transgenic reporter screens. Taken together, they provide to the scientific community many tools that could be used for drug discovery. The use of zebrafish in cancer drug screenings could help to economize time and resources even more if we rationalize its use: we could use embryonic screens to identify drugs that address general hallmarks of cancer, and use adults for finding molecules that target specific cancer models. Developmental Dynamics 242:97–107, 2013. © 2012 Wiley Periodicals, Inc.
Meiotic gene expression initiates during larval development in the sea urchinYajima, Mamiko; Suglia, Elena; Gustafson, Eric A.; Wessel, Gary M.
doi: 10.1002/dvdy.23904pmid: 23172739
Background: Meiosis is a unique mechanism in gamete production and a fundamental process shared by all sexually reproducing eukaryotes. Meiosis requires several specialized and highly conserved genes whose expression can also identify the germ cells undergoing gametogenic differentiation. Sea urchins are echinoderms, which form a phylogenetic sister group of chordates. Sea urchin embryos undergo a feeding, planktonic larval phase in which they construct an adult rudiment prior to metamorphosis. Although a series of conserved meiosis genes (e.g., dmc1, msh5, rad21, rad51, and sycp1) is expressed in sea urchin oocytes, we sought to determine when in development meiosis would first be initiated. Results: We surveyed the expression of several meiotic genes and their corresponding proteins in the sea urchin Strongylocentrotus purpuratus. Surprisingly, meiotic genes are highly expressed not only in ovaries but beginning in larvae. Both RNA and protein localizations strongly suggest that meiotic gene expression initiates in tissues that will eventually give rise to the adult rudiment of the late larva. Conclusions: These results demonstrate that broad expression of the molecules associated with meiotic differentiation initiates prior to metamorphosis and may have additional functions in these cells, or mechanisms repressing their function, until later in development when gametogenesis begins. Developmental Dynamics, 2012. © 2012 Wiley Periodicals,Inc.
Early development of the thymus in Xenopus laevisLee, Young‐Hoon; Williams, Allison; Hong, Chang‐Soo; You, Youngjae; Senoo, Makoto; Saint‐Jeannet, Jean‐Pierre
doi: 10.1002/dvdy.23905pmid: 23172757
Background: Although Xenopus laevis has been a model of choice for comparative and developmental studies of the immune system, little is known about organogenesis of the thymus, a primary lymphoid organ in vertebrates. Here we examined the expression of three transcription factors that have been functionally associated with pharyngeal gland development, gcm2, hoxa3, and foxn1, and evaluated the neural crest contribution to thymus development. Results: In most species Hoxa3 is expressed in the third pharyngeal pouch endoderm where it directs thymus formation. In Xenopus, the thymus primordium is derived from the second pharyngeal pouch endoderm, which is hoxa3‐negative, suggesting that a different mechanism regulates thymus formation in frogs. Unlike other species foxn1 is not detected in the epithelium of the pharyngeal pouch in Xenopus, rather, its expression is initiated as thymic epithelial cell starts to differentiate and express MHC class II molecules. Using transplantation experiments we show that while neural crest cells populate the thymus primordia, they are not required for the specification and initial development of this organ or for T‐cell differentiation in frogs. Conclusions: These studies provide novel information on early thymus development in Xenopus, and highlight a number of features that distinguish Xenopus from other organisms. Developmental Dynamics, 2012. © 2012 Wiley Periodicals, Inc.