Fellow's research: Fruit fly model provides molecular clues to pathology of a musculoskeletal disease

08 Apr 2019

Fellow's research: Fruit fly model provides molecular clues to pathology of a musculoskeletal disease


Dr. Sam Mathew, Intermediate Fellow

Regional Centre for Biotechnology (RCB), Faridabad

Recent research from my group has uncovered molecular mechanisms underlying Freeman-Sheldon Syndrome (FSS), a genetic disease where patients exhibit musculoskeletal abnormalities such as joint deformities, bent fingers, club feet, curved spine and facial anomalies. Patients with FSS have compromised movement; respiratory, speech and feeding problems; and delayed growth and development. Mutations in the MYH3 gene, a gene belonging to the myosin family which helps in muscle contraction, has been reported to be the primary cause of FSS. However, how mutations in the MYH3 gene leads to musculoskeletal abnormalities seen in patients with FSS is unclear.

We used the fruit fly (Drosophila melanogaster), a widely used model organism in research, to examine the muscular abnormalities that occur in patients with FSS to study genetic diseases. We generated fruit flies expressing the FSS mutant myosin and characterized the abnormalities in muscle structure and function. The muscle is made up of numerous muscle fibres, which in turn contain sarcomeres, the functional contractile units of the muscle. We find that expressing the FSS mutant myosin leads to severe muscle defects such as shortening of the length and width of the sarcomeres, splitting of muscle fibres, aberrant muscle contraction, and reduced climbing capability. Interestingly, these defects became more severe with age and muscle use.

Thus, using the fruit fly, we have characterized what goes wrong in the muscle of patients with FSS. Using this disease model, we would now like to identify potential strategies to alleviate muscle defects, which should provide new approaches to treating patients born with this disorder.


Myosin heavy chain mutations that cause Freeman-Sheldon Syndrome lead to muscle structural and functional defects in Drosophila. Das, S., Kumar, P., Verma, A., Maiti, T.K., and Mathew, S.J. Developmental Biology, May 2019

Banner Image: Indirect flight muscles of 20-day old Drosophila expressing myosin heavy chain, labelled by immunofluorescence for the Z-disc (red), thin filaments (green), and nuclei (blue). Credits: Dr Sam Mathew