The Amaya Lab
The molecular and cellular basis of tissue repair and regeneration
Amphibian embryos have an incredible ability to heal following manipulations, which is one of the primary reasons why they have been used for more than a century as an experimental embryological system. Xenopus embryos are able to heal following wounding within hours, without leaving a scar or any sign of damage. In order to identify new genes involved in wound healing, we plan to perform large-scale screens aimed at identifying genes, which either promote or delay healing in embryos. In addition, we have begun to investigate the development of primitive myeloid cells in Xenopus and have been studying their role during embryonic wound healing. Finally, Xenopus tadpoles are able to regenerate all the tissues in the tail, following amputation, within nine days. We are using functional genomic approaches to identify novel genes involved in the regeneration of all the tissue types in the tail, which include the vasculature, muscle, spinal chord and the notochord. The ultimate aim of this work is to identify new gene targets, which may form the basis of novel therapeutic and clinical applications to wound healing and tissue regeneration.
FGF receptor signalling in early development
One of the main interests of our group is understanding the molecular events responsible for mesoderm formation and patterning. In particular we are investigating the role of fibroblast growth factor (FGF) signalling during mesoderm formation in the frog, Xenopus. We have shown that inhibiting FGF signalling during gastrulation disrupts mesoderm specification and morphogenesis. In order to better understand these processes, we have begun to isolate downstream targets of FGF signalling. We have identified Xsprouty2 as an important target gene. This protein and the related proteins, Xsprouty1, Xspred1 and Xspred2 are both targets and modulators of FGF signaling. We have recently shown that the Sprouty and Spred proteins play an important role in FGF signal interpretation, allowing mesoderm specification and morphogenesis to occur in a coordinate fashion.
Functional genomics in Xenopus tropicalis
In order to identify additional genes involved in mesoderm specification and morphogenesis, we have been developing genomic resources and bioinformatics tools, in combination with functional screens, to identify additional genes involved in these processes. As part of this project we have identified over 7000 full-length clones from Xenopus tropicalis and have screened nearly 2000 of these clones for genes affecting mesoderm formation and/or morphogenesis. Of those tested, we have isolated 82 genes, which alter or inhibit mesoderm formation and/or gastrulation movements.
Patterning of the nervous system
We are investigating the molecular basis of neural patterning in Xenopus. In a recent large scale functional screen we identified a novel D-type cyclin, which is essential for the specification and maintenance of the precursors of motor neurons (pMNs) within the spinal chord in Xenopus. In addition, we have been investigating the role of neurotrophic factors in the pathfinding of the trigeminal nerves.
Latest Publications
Love, N.R., Thuret, R., Chen, Y., Ishibashi, I., Sabherwal, N., Paredes, R., Alves-Silva, J., Noble, A.M., Guille, M.J., Sasai, Y., Papalopulu, N. and Amaya, E. (2011) pTransgenesis: a cross-species, modular transgenesis resource. Development 138(24):5451-8.
Love, N.R., Chen, Y., Bonev, B., Gilchrist, M.J., Fairclough, L., Lea, R., Mohun, T.J., Paredes, R., Zeef, L.A.H, and Amaya, E. (2011) Genome-wide analysis of gene expression during Xenopus tropicalis tadpole tail regeneration. BMC Developmental Biology 11:70.
Panagiotaki, N., Dajas-Bailador, F., Amaya, E., Papalopulu, N. & Dorey, K. (2010). Characterisation of a new regulator of BDNF signalling, Sprouty3, involved in axonal morphogenesis in vivo. Development, 137(23), 4005-4015.
Göttgens, B., Ferreira, R., Sanchez, M., Ishibashi, S., Li, J., Spensberger, D., Lefevre, P., Ottersbach, K., Chapman, M., Kinston, S., Knezevic, K., Hoogenkamp, M., Follows, G., Bonifer, C., Amaya, E. & Green, A. (2010). cis-Regulatory Remodeling of the SCL Locus during Vertebrate Evolution. Mol Cell Biol, 30(24), 5741-51.
Dorey, K. & Amaya, E. (2010). FGF signalling: diverse roles during early vertebrate embryogenesis. Development, 137(22), 3731-42.
People
- Enrique Amaya
- Shoko Ishibashi
- Ximena Soto
- Roberto Paredes
- Nick Love
- Robert Lea
- Yanan Zhao
- Jingjing Li
- Siwei Zhang
- Yue Han
- Yvette Koh