Dr Leslie Dale
We are interested in how the embryo of the frog Xenopus laevis develops from a fertilized egg into a swimming tadpole. Xenopus embryos have many advantages as a model for studying cell signalling during development: Large numbers of synchronously developing embryos are easily obtained and their large size and ease of culture means that they are amenable to micromanipulation and single cell injection. Workable transgenic protocols have been developed and there has been some success in inhibiting gene function with antisense technologies. As a consequence, studies on Xenopus embryos have made many important contributions to our understanding of vertebrate development.
Partial duplicated dorsal axis caused by ventral injection of mRNA for dominant-negative BMP1, which inhibits all three Tolloid metalloproteases
Whole mount in situ hybridisations showing the expression pattern of xolloid-related in Xenopus embryos
Whole mount in situ hybridisation showing p2y8 expression in Xenopus neurulae
G-Protein Coupled Receptors
The GPCR family is the largest family of cell-surface receptors, with thousands already described. In mice there are about 1000 GPCRs concerned with the sense of smell alone. They act as receptors for an enormous range of signals, including proteins, small peptides, amino acids, fatty acids, and nucleotides. All have a similar structure, a single polypeptide chain that threads back and forth across the lipid bilayer seven times, with an extracellular N-terminus and an intracellular C-terminus. They all activate trimeric GTP-binding proteins (G-proteins), relay molecules that activate a number of intracellular effector molecules (e.g. Ca2+ and cAMP).Despite their importance in adult physiology, relatively little is known about their roles in development. We have previously cloned a GPCR for extracellular nucleotides (e.g. ATP) that we have called P2Y8 and shown that it is localised to the developing neural plate. Transcripts are lost once the neural tube has formed, indicating that it has a role in the earliest phase of neural development. We have searched the Xenopus EST databases for GPCRs that are expressed during early developemnt, concentrating on receptors belonging to the P2Y subclass. At least four P2Y receptors are expressed in Xenopus gastrulae and we are currently characterising their roles in development.
Dale, Evans, Goodman (2002) Xolloid-related: A novel BMP1/Tolloid-related metalloprotease is expressed during early Xenopus development. Mech Dev 119: 177-190.
Dale, Jones (1999) BMP signalling in early Xenopus development. BioEssays 21:751-760.
Piccolo, Agius, Lu, Goodman, Dale, DeRobertis (1997) Cleavage of chordin by Xolloid metalloprotease suggests a role for proteolytic processing in the regulation of Spemann organizer activity. Cell 91: 407-416
Bogdonov, Dale, King, Whittock, Burnstock (1997) Early expression of a novel nucleotide receptor in the neural plate of Xenopus embryos. J Biol Chem 272: 12583-12590.
Dr Leslie Dale
|+44 (0)20 7679 3061|
|hristelle Devader (Research Assistant)||+44 (0)20 7679 3367|
|Tim Geach (PhD Student)||+44 (0)20 7679 3367|
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