Muscle and limb/fin development and evolution
Head of laboratory:
Initiation, specification and control of vertebrate limb and muscle development.
The general aim of my research is to generate a detailed understanding of the morphological and genetic control of precursor specification, migration and proliferation that is deployed to generate vertebrate limbs and muscle. The fundamental question of how different populations form within an embryo has until now, been extremely difficult to address in conventional systems purely due to logistical constraints; mammalian embryos develop in- utero, and direct visual observation of living muscle is all but impossible. In contrast, the zebrafish develops ex-utero and is optically clear during the embryonic and juvenile stages- yielding a unique possibility to examine development in vivo.
The muscle structure of zebrafish represents a relatively simple paradigm where muscle precursors specification and subsequent myoblast elongation, fusion and attachment can be followed in real time using time-lapse photo microscopy. Just as in human embryos, the appendicular muscles of zebrafish are formed from populations of long-range migrating precursors that originate in the somites and express the gene lbx1. In addition, our limbs evolved from the paired fins of ancestral fish, such that initiation and outgrowth of fins is genetically similar to early limb formation. These characteristics make zebrafish a powerful and genetically tractable model system for the analysis of vertebrate limb initiation and muscle development.
The long-term outcome of this work will enhance our understanding of limb formation and how stem cell-driven muscle formation and repair occurs in vertebrate embryos. This knowledge will have profound implications for our understanding of the pathology and treatment of limb developmental defects and degenerative muscle disease.
Projects will involve developmental and molecular biology, incorporating modern research techniques (in-situ hybridisation, confocal and electron microscopy, PCR, bioinformatics, fish husbandry, transgenic fish technology, immuno-histochemistry, histology, in-vivo cell lineage tracking) and utilising the zebrafish model system.
