Initiation, specification and control of vertebrate limb and muscle development.

Summary

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 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. 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 formation and repair occurs in vertebrate embryos. This knowledge will have profound implications for our understanding of limb development.

Supervisor(s)

Dr Nicholas Cole

Research Location

Camperdown - School of Medical Sciences - Bosch Institute

Program Type

Masters/PHD

Synopsis

The general aim of my research is to generate a detailed understanding of the morphological and genetic control of limb development and muscle formation by examining these proceses in fish. Our limbs are evolutionarily derived from the fins of ancestral fish. As a result similar gene expression patterns and cellular control is deployed to generate the fins and muscle of fish and the limbs and muscles of man. By understanding the normal processes occuring during fish development we are able to determine the mechanisms at work during normal growth and importantly during  disease states in ourselves (humans). I fucus upon the 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.*Evolutionary origins of vertebrate limb musculature and the tetrapod transition.Locomotor strategies in terrestrial tetrapod species have evolved from the utilisation of sinusoidal contractions of axial musculature, evident in ancestral fish species, to the reliance on powerful and complex limb muscles to provide propulsive force. Within tetrapod species, a hind limb-dominant locomotor strategy predominates, and its evolution is considered critical for the evident success of the tetrapod transition on to land. A number of fossil forms have provided information on the evolution of the appendicular skeleton of the hind limbs within early tetrapods. Although the fossil record has, in part, charted the evolution of the skeletal framework of the load bearing limbs of tetrapods, it can shed little light on how the accompanying dramatic alterations of the limb musculature required to drive locomotion in terrestrial tetrapods have arisen, as soft tissues are rarely preserved within the fossil record. In order to examine this question it is necessary to uncover the mechanisms that generate limb and fin muscles within extant species strategically positioned within the vertebrate phylogeny. We are examining this question by describing the mechanisms utilised to generate fin muscles within extant fish species positioned at critical points within the vertebrate phylogeny (sharks, paddlefish and lungfish).

Additional Information

Zebrafish are our model organism, increadibly these small fish are an amazing system to answer many questions of human disease. The laboratory has a brand new 'state of the art zebrafish facility'. In addition I examine sharks, paddlefish and lungfish for an evolutionary view point. I will provide an encouraging, interactive and enjoyable environment for you to development as a research scientist. I am very open to your own ideas and questions.
Please note that you will require a a scholarship to perform this exciting research.

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Keywords

muscle, limb, zebrafish, Evolution, gene expression, craniofacial, Dr Nicholas Cole

Opportunity ID

The opportunity ID for this research opportunity is: 921

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