Knockdown of pnpla6 protein results in motor neuron defects in zebrafish
- Authors
- Song, Y., Wang, M., Mao, F., Shao, M., Zhao, B., Song, Z., Shao, C., and Gong, Y.
- ID
- ZDB-PUB-121004-11
- Date
- 2013
- Source
- Disease models & mechanisms 6(2): 404-413 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Up-Regulation/drug effects
- Cells, Cultured
- Phenotype
- Sensory Receptor Cells/drug effects
- Sensory Receptor Cells/metabolism
- Sensory Receptor Cells/pathology
- Mutant Proteins/genetics
- Mutant Proteins/metabolism
- Interneurons/drug effects
- Interneurons/metabolism
- Interneurons/pathology
- Zebrafish/embryology
- Zebrafish/metabolism*
- Humans
- Axons/metabolism
- Axons/pathology
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/metabolism*
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/enzymology
- Embryo, Nonmammalian/pathology
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Molecular Sequence Data
- Mice
- Morpholinos/pharmacology
- Amino Acid Sequence
- Gene Knockdown Techniques*
- Animals
- Phospholipases A2, Calcium-Independent/chemistry
- Phospholipases A2, Calcium-Independent/metabolism*
- Bone Morphogenetic Proteins/metabolism
- Signal Transduction/drug effects
- Phospholipases/chemistry
- Phospholipases/metabolism*
- Motor Neurons/drug effects
- Motor Neurons/enzymology*
- Motor Neurons/pathology*
- PubMed
- 22996643 Full text @ Dis. Model. Mech.
Mutations in patatin-like phospholipase domain containing 6 (PNPLA6), also known as neuropathy target esterase (NTE), or SPG39, cause hereditary spastic paraplegia (HSP). Although studies on animal models including mice and Drosophila have extended our understanding of PNPLA6, its role in neural development and HSP is not clearly understood. Here, we generated a vertebrate model of PNPLA6 insufficiency using morpholino oligonucleotide knockdown in zebrafish (Danio rerio). PNPLA6 knockdown results in developmental abnormalities and motor neuron defects including axon truncation and branching. The phenotypes in pnpla6 knockdown morphants can be rescued by introduction of wide type (WT), but not mutant, human PNPLA6 mRNA. Our results also revealed the involvement of BMP signaling in pnpla6 knockdown phenotypes. Taken together, these results demonstrated an important role of PNPLA6 in motor neuron development and implicated overexpression of BMP signaling as the possible mechanism underlying the developmental defects in pnpla6 morphants.