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
-
- Amino Acid Sequence
- Animals
- Axons/metabolism
- Axons/pathology
- Bone Morphogenetic Proteins/metabolism
- Cells, Cultured
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/enzymology
- Embryo, Nonmammalian/pathology
- Gene Knockdown Techniques*
- Humans
- Interneurons/drug effects
- Interneurons/metabolism
- Interneurons/pathology
- Mice
- Molecular Sequence Data
- Morpholinos/pharmacology
- Motor Neurons/drug effects
- Motor Neurons/enzymology*
- Motor Neurons/pathology*
- Mutant Proteins/genetics
- Mutant Proteins/metabolism
- Phenotype
- Phospholipases/chemistry
- Phospholipases/metabolism*
- Phospholipases A2, Calcium-Independent/chemistry
- Phospholipases A2, Calcium-Independent/metabolism*
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Sensory Receptor Cells/drug effects
- Sensory Receptor Cells/metabolism
- Sensory Receptor Cells/pathology
- Signal Transduction/drug effects
- Up-Regulation/drug effects
- Zebrafish/embryology
- Zebrafish/metabolism*
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/metabolism*
- 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.