This project would establish a national Xenopus Resource Center at the Marine Biological Laboratory (MBL) in Woods Hole, MA. White Papers submitted to NIH by the Xenopus research community describe the urgent need for a center to house animal stocks and to disseminate new technology. Several laboratories, primarily those who are key personnel on this proposal, have defined the husbandry, health and housing conditions needed to develop a major stock center. The MBL is an ideal place for such a center because it is acknowledged as a premier site for biological research;it has a long association with the Xenopus research community and, as part of a Regenerative Medicine initiative, will fund the construction of a new Xenopus Center if funds are obtained for Center operation in 2009. This resubmission has four aims. The first entails setting up the facility in year 1 and generating critical animal lines (wildtype, inbred, transgenic and mutant).
In aim 2, covering years 2-5, the scope of the facility will be expanded, to provide a spectrum of animal lines recognized as a high priority by the research community. In addition, transgenic and genetic core facilities will be established as part of the new Center to allow new lines to be generated, and for researchers to visit the facility to learn technologies associated with these areas. In the third aim, we focus on the role of the proposed Center in disseminating new technology This would include a series of minicourses to be offered at the Center, to be taught by experts in particular areas (e.g. husbandry, transgenesis, advanced imaging, preparation of egg extracts, bioinformatics).
The final aim focuses on animal husbandry, include setting up protocols for enhanced husbandry and health surveillance, and disseminating these to the research community. Experiments are proposed to optimize husbandry to improve fertility of females and shorten the time to sexual maturity. Some key changes in this resubmission are: 1) an increased emphasis on X. laevis stocks (and concomitant reduction of X. tropicalis stocks) in order to better serve community needs;2) development of a clearer leadership plan;3) reduction in the complexity of aims (e.g. reducing stock number in the Center;removing forward genetics core);and 4) clarification of health and disease outbreak issues.
Cell biologists studying Xenopus have made many breakthroughs in our understanding of cell adhesion and movements, signal transduction and control of the cell cycle, and thus to our understanding of cancer biology, because malignant transformation affects all of these processes in fundamental ways. Developmental biologists studying Xenopus have made transformative insights into processes controlling patterning of and movements in the embryo. and gene regulation, which underlie a multitude of birth defects.
|Steimle, Jeffrey D; Rankin, Scott A; Slagle, Christopher E et al. (2018) Evolutionarily conserved Tbx5-Wnt2/2b pathway orchestrates cardiopulmonary development. Proc Natl Acad Sci U S A 115:E10615-E10624|
|DeLay, Bridget D; Corkins, Mark E; Hanania, Hannah L et al. (2018) Tissue-Specific Gene Inactivation in Xenopus laevis: Knockout of lhx1 in the Kidney with CRISPR/Cas9. Genetics 208:673-686|
|Wlizla, Marcin; Falco, Rosalia; Peshkin, Leonid et al. (2017) Luteinizing Hormone is an effective replacement for hCG to induce ovulation in Xenopus. Dev Biol 426:442-448|
|Pearl, Esther; Morrow, Sean; Noble, Anna et al. (2017) An optimized method for cryogenic storage of Xenopus sperm to maximise the effectiveness of research using genetically altered frogs. Theriogenology 92:149-155|
|Ratzan, Wil; Falco, Rosalia; Salanga, Cristy et al. (2017) Generation of a Xenopus laevis F1 albino J strain by genome editing and oocyte host-transfer. Dev Biol 426:188-193|
|Savova, Virginia; Pearl, Esther J; Boke, Elvan et al. (2017) Transcriptomic insights into genetic diversity of protein-coding genes in X. laevis. Dev Biol 424:181-188|
|Webb, Bryn D; Metikala, Sanjeeva; Wheeler, Patricia G et al. (2017) Heterozygous Pathogenic Variant in DACT1 Causes an Autosomal-Dominant Syndrome with Features Overlapping Townes-Brocks Syndrome. Hum Mutat 38:373-377|
|Tandon, Panna; Conlon, Frank; Furlow, J David et al. (2017) Expanding the genetic toolkit in Xenopus: Approaches and opportunities for human disease modeling. Dev Biol 426:325-335|
|Sedzinski, Jakub; Hannezo, Edouard; Tu, Fan et al. (2016) Emergence of an Apical Epithelial Cell Surface In Vivo. Dev Cell 36:24-35|
|Vukovi?, Lidija D; Jevti?, Predrag; Zhang, Zhaojie et al. (2016) Nuclear size is sensitive to NTF2 protein levels in a manner dependent on Ran binding. J Cell Sci 129:1115-27|
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