ANALYSIS OF AXONAL TRANSPORT DEFECTS IN A ZEBRAFISH MODEL FOR SPINAL MUSCULAR ATROPHY
Spinal muscular atrophy (SMA) is an autosomal recessive hereditary neurodegenerative disease caused by a deficiency of the survival motor neuron (SMN) protein. It is characterised by the progressive loss of α-motor neurons (MNs), leading to muscle weakness, atrophy, and in the worst cases death. SMN is a ubiquitously expressed protein that is involved in spliceosome assembly. A decrease in SMN protein levels leads to the dysregulation of splicing of downstream genes and thereby impairs cellular processes that most prominently affect MNs. Speculations as to the cause of this specific vulnerability of MNs include the selective aberrant splicing of critical MN-specific transcripts and an increased sensitivity to axonal transport deficiencies. The splicing factor Srsf6b and motor adaptor protein Fez1 are two candidate target proteins for SMN in these processes, respectively. I aimed to study the roles of these proteins in order to better understand the processes underlying SMA pathology.
axonal transport, zebrafish, motor neurons, FEZ1, SMN, spinal muscular atrophy
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