title: Knockdown of Pnpla6 protein results in motor neuron defects in zebrafish.
abstract: 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 roles in neural development and in HSP are not clearly understood. Here, we describe the generation of a vertebrate model of PNPLA6 insufficiency using morpholino oligonucleotide knockdown in zebrafish (Danio rerio). Pnpla6 knockdown resulted in developmental abnormalities and motor neuron defects, including axon truncation and branching. The phenotypes in pnpla6 knockdown morphants were rescued by the introduction of wild-type, but not mutant, human PNPLA6 mRNA. Our results also revealed the involvement of BMP signaling in pnpla6 knockdown phenotypes. Taken together, these results demonstrate an important role of PNPLA6 in motor neuron development and implicate overexpression of BMP signaling as a possible mechanism underlying the developmental defects in pnpla6 morphants.
authors.affiliation: Institute of Medical Genetics and Key Laboratory for Experimental Teratology of Ministry of Education, School of Medicine, Shandong University, Jinan 250012 Shandong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.forename: Molin
authors.initials: M
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Mao
authors.forename: Ming
authors.initials: M
authors.lastname: Shao
authors.forename: Baochang
authors.initials: B
authors.lastname: Zhao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Song
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
authors.forename: Yaoqin
authors.initials: Y
authors.lastname: Gong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D055785:Gene Knockdown Techniques; D006801:Humans; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D010740:Phospholipases / Q000737:chemistry / Q000378:metabolism*; D054512:Phospholipases A2, Calcium-Independent / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000378:metabolism*; D000217:Acyltransferases
chemical_list: D019485:Bone Morphogenetic Proteins; D060172:Morpholinos; D050505:Mutant Proteins; D010740:Phospholipases; D054512:Phospholipases A2, Calcium-Independent; D012333:RNA, Messenger; D029961:Zebrafish Proteins; C583357:PNPLA6 protein, zebrafish; D000217:Acyltransferases