Related Experiment Video
Updated: May 30, 2026
Facial Nerve Axotomy in Mice: A Model to Study Motoneuron Response to Injury
Published on: February 23, 2015
Motoneuron programmed cell death in response to proBDNF
Anna R Taylor1, David J Gifondorwa, Mac B Robinson
1Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Abstract:
Motoneurons (MN) as well as most neuronal populations undergo a temporally and spatially specific period of programmed cell death (PCD). Several factors have been considered to regulate the survival of MNs during this period, including availability of muscle-derived trophic support and activity. The possibility that target-derived factors may also negatively regulate MN survival has been considered, but not pursued. Neurotrophin precursors, through their interaction with p75(NTR) and sortilin receptors have been shown to induce cell death during development and following injury in the CNS. In this study, we find that muscle cells produce and secrete proBDNF. ProBDNF through its interaction with p75(NTR) and sortilin, promotes a caspase-dependent death of MNs in culture. We also provide data to suggest that proBDNF regulates MN PCD during development in vivo.
Insights
Muscle cells secrete pro-brain-derived neurotrophic factor (proBDNF), which triggers programmed cell death (PCD) in motoneurons (MNs) via specific receptors. This study reveals a novel mechanism regulating MN survival during development.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Motoneurons (MNs) undergo programmed cell death (PCD) during development, influenced by trophic support and activity.
- The role of target-derived factors in negatively regulating MN survival is less understood.
- Neurotrophin precursors interacting with p75(NTR) and sortilin receptors can induce neuronal death.
Purpose of the Study:
- To investigate the role of muscle-derived factors in regulating motoneuron survival.
- To determine if pro-brain-derived neurotrophic factor (proBDNF) contributes to motoneuron PCD.
- To elucidate the mechanisms by which proBDNF affects motoneuron survival.
Main Methods:
- In vitro culture of motoneurons.
- Analysis of proBDNF production and secretion by muscle cells.
- Investigating the interaction of proBDNF with p75(NTR) and sortilin receptors.
- Assessing caspase-dependent cell death pathways.
- In vivo studies during motoneuron development.
Main Results:
- Muscle cells were found to produce and secrete proBDNF.
- ProBDNF, in conjunction with p75(NTR) and sortilin, induced caspase-dependent death in cultured motoneurons.
- Evidence suggests proBDNF regulates motoneuron PCD during development in vivo.
Conclusions:
- Muscle-derived proBDNF acts as a death signal for motoneurons.
- The interaction of proBDNF with p75(NTR) and sortilin mediates motoneuron apoptosis.
- ProBDNF plays a significant role in regulating motoneuron survival during development.
Related Concept Videos
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
01:16Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
01:18Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...