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Immunolabelling Myofiber Degeneration in Muscle Biopsies
Published on: December 5, 2019
Cell death regulates muscle fiber number
Tatevik Sarkissian1, Richa Arya1, Seda Gyonjyan1
1CBRC, Massachusetts General Hospital Research Institute/Harvard Medical School, Boston, MA 02129, USA.
Abstract:
Cell death can have both cell autonomous and non-autonomous roles in normal development. Previous studies have shown that the central cell death regulators grim and reaper are required for the developmentally important elimination of stem cells and neurons in the developing central nervous system (CNS). Here we show that cell death in the nervous system is also required for normal muscle development. In the absence of grim and reaper, there is an increase in the number of fibers in the ventral abdominal muscles in the Drosophila adult. This phenotype can be partially recapitulated by inhibition of cell death specifically in the CNS, indicating a non-autonomous role for neuronal death in limiting muscle fiber number. We also show that FGFs produced in the cell death defective nervous system are required for the increase in muscle fiber number. Cell death in the muscle lineage during pupal stages also plays a role in specifying fiber number. Our work suggests that FGFs from the CNS act as a survival signal for muscle founder cells. Thus, proper muscle fiber specification requires cell death in both the nervous system and in the developing muscle itself.
Insights
Cell death in the nervous system and muscles is crucial for normal development. This study reveals that neuronal cell death non-autonomously regulates muscle fiber number via FGF signaling in Drosophila.
Area of Science:
- Developmental Biology
- Neuroscience
- Cell Biology
Background:
- Cell death plays vital roles in development, including eliminating stem cells and neurons.
- Central cell death regulators grim and reaper are essential for CNS development.
Purpose of the Study:
- To investigate the role of neuronal cell death in muscle development.
- To elucidate the mechanisms by which neuronal cell death influences muscle fiber number.
Main Methods:
- Utilized Drosophila melanogaster as a model organism.
- Genetically manipulated cell death regulators (grim and reaper).
- Assessed muscle fiber number and FGF signaling pathways.
Main Results:
- Absence of grim and reaper led to increased muscle fiber number in adult Drosophila.
- Inhibiting CNS cell death partially mimicked this phenotype, indicating a non-autonomous role.
- FGFs from the CNS were essential for the increased muscle fiber number.
- Cell death within the muscle lineage also impacts fiber specification.
Conclusions:
- Neuronal cell death non-autonomously limits muscle fiber number.
- FGF signaling from the CNS acts as a survival signal for muscle founder cells.
- Proper muscle fiber specification requires coordinated cell death in both the nervous system and muscle.
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