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School of Biosciences, Division of
Animal Sciences
   
   
  
 

Dylan Sweetman

Lecturer in Molecular Embryology, Faculty of Science

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Research Summary

Research summary: The focus of my research is understanding embryonic development, primarily using the chicken embryo as a model system.

MicroRNAs in limb muscle development:

microRNAs (miRs) are small non coding RNAs which regulate gene expression during development. I have previously worked on muscle specific microRNAs during development in Andrea Münsterberg's lab.

Using LNA modified oligonucleotides it is possible to detect expression of these miRs during development and they are expressed during embryonic development of several vertebrates including chicken, mouse, Xenopus and zebrafish. In embryos of all these species these miRs are expressed in somites, the embryonic structures which produce muscle.

My previous work at the University of East Anglia showed that these miRs are regulated by FGF signaling, probably via the MRF transcription factors, in vivo. Interestingly the limb muscles have different regulatory mechanisms controlling miR expression and we believe that the miRs will also play a distinct role in controlling the development of these muscle types. In the future the study of the regulation and function of these molecules in limb buds should provide important insights into the developmental programmes which regulate this group of muscles.

Development of limb muscles:

During development trunk muscle cells are generated in somites, transient segmental embryonic structures which arise from paraxial mesoderm. The dorsal region of the somite gives rise to the dermomyotome which will produce both dermis and muscle. The earliest marker of muscle cells in the dermomyotome is the transcription factor Pax3. Differentiation of these cells is induced by Wnt and Shh signals from the neural tube, ectoderm and notochord. Epaxial muscle forms when Pax3 positive cells migrate to form a layer under the dermomytome, the myotome, where they differentiate and begin to express muscle specific genes such as MRFs and sarcomeric myosin.

Limb muscle cells also express Pax3 but delaminate from the ventro-lateral region of the dermomyotome and migrate into the limb buds where they form the dorsal and ventral muscle masses. Only then do these cells begin to differentiate and express muscle specific markers. We are interested in the signals which drive differentiation of these cells in the limb bud. It is clear that the limb muscle cells do not simply recapitulate the trunk myogenic programme; while there are many common features there are also limb and trunk specific aspects. We hope that understanding these genetic programmes will help in designing treatments for muscle diseases and injury.

Work on the developmental programming of limb muscles is currently being carried out by Gi Fay (Geoffrey) Mok for his PhD in Animal Sciences

Recent Publications

Past Research

Previous postdoctoral research in Andrea Münsterberg's lab at the UEA has included studies on the spalt family of transcription factors, particularly their roles in limb development and Townes-Brocks syndrome. I have also worked on Wnt signalling in gastrulation at neurula stage embryos.

Division of Animal Sciences

University of Nottingham
Sutton Bonington Campus
Loughborough, Leicestershire LE12 5RD

telephone: +44 (0) 115 951 6100
email: sheila.northover@nottingham.ac.uk