PositionReader in Developmental Biology
We are interested in how the embryo of the frog Xenopus laevis develops from a fertilized egg into a swimming tadpole. Our current research has focussed on the roles of two gene families: the Tolloid family of metalloproteases and the P2Y family of G-protein coupled receptors (GPCRs). We have identified 3 members of the Tolloid family in early Xenopus embryos and shown that they are required for dorsal-ventral patterning during gastrulation. Increasing activity ventralizes embryos while decreasing activity dorsalizes them. We have shown that their function is to modulate the activity of BMP4, a key ventralizing signal, by cleaving Chordin, a BMP inhibitor. Cleavage by Tolloids reduces the affinity of Chordin for BMPs, thereby increasing BMP activity. A second project explores the roles of members of the P2Y family in Xenopus development. We have cloned several members of this family that are expressed in Xenopus embryos and shown that two of them (P2Y8 AND P2Y11) are receptors for extracellular nucleotides (e.g. ATP). Inhibition of the latter generates defects in several tissues, including the nervous system. We have also shown that P2Y5, an orphan receptor, is required in brain development. Recently, we have begun a collaborative project with the laboratory of Dr S Patel, characterising Xenopus ADP-Ribosyl cyclases. These enzymes synthesize calcium releasing second messengers such as cADPR and NAADP. We have evidence that they are required for differentiation of skeketal muscle in Xenopus embryos.
Lab MembershipsDale Laboratory (Principal Investigator/Director)
British Xenopus Group (Other)
Research Department of Cell and Developmental Biology
University College London
WC1E 6BT, United Kingdom