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Drosophila Graf regulates mushroom body beta-axon extension and olfactory long-term memory

Authors
Kim, SungdaeKim, JoohyungPark, SunyoungPark, Joong-JeanLee, Seungbok
Issue Date
23-4월-2021
Publisher
BMC
Keywords
Drosophila; EGFR signaling; Graf; Intellectual disability; Mushroom body development; oligophrenin-1
Citation
MOLECULAR BRAIN, v.14, no.1
Indexed
SCIE
SCOPUS
Journal Title
MOLECULAR BRAIN
Volume
14
Number
1
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/137448
DOI
10.1186/s13041-021-00782-x
ISSN
1756-6606
Abstract
Loss-of-function mutations in the human oligophrenin-1 (OPHN1) gene cause intellectual disability, a prevailing neurodevelopmental condition. However, the role OPHN1 plays during neuronal development is not well understood. We investigated the role of the Drosophila OPHN1 ortholog Graf in the development of the mushroom body (MB), a key brain structure for learning and memory in insects. We show that loss of Graf causes abnormal crossing of the MB beta lobe over the brain midline during metamorphosis. This defect in Graf mutants is rescued by MB-specific expression of Graf and OPHN1. Furthermore, MB alpha/beta neuron-specific RNA interference experiments and mosaic analyses indicate that Graf acts via a cell-autonomous mechanism. Consistent with the negative regulation of epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) signaling by Graf, activation of this pathway is required for the beta-lobe midline-crossing phenotype of Graf mutants. Finally, Graf mutants have impaired olfactory long-term memory. Our findings reveal a role for Graf in MB axon development and suggest potential neurodevelopmental functions of human OPHN1.
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