title: Drp1-mediated mitochondrial dynamics and survival of developing chick motoneurons during the period of normal programmed cell death.
abstract: Mitochondrial morphology is dynamically remodeled by fusion and fission in neurons, and this process is implicated in nervous system development and pathology. However, the mechanism by which mitochondrial dynamics influence neuronal development is less clear. In this study, we found that the length of mitochondria is progressively reduced during normal development of chick embryo motoneurons (MNs), a process partly controlled by a fission-promoting protein, dynamin-related protein 1 (Drp1). Suppression of Drp1 activity by gene electroporation of dominant-negative mutant Drp1 in a subset of developing MNs increased mitochondrial length in vivo, and a greater proportion of Drp1-suppressed MNs underwent programmed cell death (PCD). By contrast, the survival of nontransfected MNs in proximity to the transfected MNs was significantly increased, suggesting that the suppression of Drp1 confers disadvantage during the competition for limited survival signals. Because we also monitored perturbation of neurite outgrowth and mitochondrial membrane depolarization following Drp1 suppression, we suggest that impairments of ATP production and axonal growth may be downstream factors that influence the competition of MNs for survival. Collectively, these results indicate that mitochondrial dynamics are required for normal axonal development and competition-dependent MN PCD.
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
authors.forename: So Yoen
authors.initials: SY
authors.lastname: Choi
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Hyun-Wook
authors.initials: HW
authors.lastname: Kim
authors.forename: Bongki
authors.initials: B
authors.lastname: Cho
authors.forename: Hyo Min
authors.initials: HM
authors.lastname: Cho
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Oppenheim
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.forename: Im Joo
authors.initials: IJ
authors.lastname: Rhyu
authors.forename: Woong
authors.initials: W
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002470:Cell Survival; D002642:Chick Embryo; D017931:DNA Primers; D034281:Dynamins / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008855:Microscopy, Electron, Scanning; D008928:Mitochondria / Q000502:physiology*; D009046:Motor Neurons / Q000166:cytology*; D060888:Real-Time Polymerase Chain Reaction; D013116:Spinal Cord / Q000166:cytology
chemical_list: D017931:DNA Primers; D034281:Dynamins