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Neuron‐specific knockdown of the Drosophila fat induces reduction of life span, deficient locomotive ability, shortening of motoneuron terminal branches and defects in axonal targeting
Author(s) -
Nakamura Aya,
Tanaka Ryo,
Morishita Kazushige,
Yoshida Hideki,
Higuchi Yujiro,
Takashima Hiroshi,
Yamaguchi Masamitsu
Publication year - 2017
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12500
Subject(s) - biology , gene knockdown , neuron , microbiology and biotechnology , synapse , gene , neuroscience , genetics
Mutations in FAT 4 gene, one of the human FAT family genes, have been identified in Van Maldergem syndrome ( VMS ) and Hennekam lymphangiectasia‐lymphedema syndrome ( HS ). The FAT 4 gene encodes a large protein with extracellular cadherin repeats, EGF ‐like domains and Laminin G‐like domains. FAT 4 plays a role in tumor suppression and planar cell polarity. Drosophila contains a human FAT 4 homologue, fat. Drosophila fat has been mainly studied with Drosophila eye and wing systems. Here, we specially knocked down Drosophila fat in nerve system. Neuron‐specific knockdown of fat shortened the life span and induced the defect in locomotive abilities of adult flies. In consistent with these phenotypes, defects in synapse structure at neuromuscular junction were observed in neuron‐specific fat ‐knockdown flies. In addition, aberrations in axonal targeting of photoreceptor neuron in third‐instar larvae were also observed, suggesting that fat involves in axonal targeting. Taken together, the results indicate that Drosophila fat plays an essential role in formation and/or maintenance of neuron. Both VMS and HS show mental retardation and neuronal defects. We therefore consider that these two rare human diseases could possibly be caused by the defect in FAT 4 function in neuronal cells.