Drosophila Netrin-B controls mushroom body axon extension and regulates courtship-associated learning and memory of a Drosophila fragile X syndrome model

Abstract Mushroom body (MB) is a prominent structure essential for olfactory learning and memory in the Drosophila brain. The development of the MB involves the appropriate guidance of axon lobes and sister axon branches. Appropriate guidance that accurately shapes MB development requires the integr...

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Main Authors: Huaixing Kang, Juan Zhao, Xuan Jiang, Guangxu Li, Wen Huang, Huili Cheng, Ranhui Duan
Format: Article
Language:English
Published: BMC 2019-05-01
Series:Molecular Brain
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13041-019-0472-1
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author Huaixing Kang
Juan Zhao
Xuan Jiang
Guangxu Li
Wen Huang
Huili Cheng
Ranhui Duan
author_facet Huaixing Kang
Juan Zhao
Xuan Jiang
Guangxu Li
Wen Huang
Huili Cheng
Ranhui Duan
author_sort Huaixing Kang
collection DOAJ
description Abstract Mushroom body (MB) is a prominent structure essential for olfactory learning and memory in the Drosophila brain. The development of the MB involves the appropriate guidance of axon lobes and sister axon branches. Appropriate guidance that accurately shapes MB development requires the integration of various guidance cues provided by a series of cell types, which guide axons to reach their final positions within the MB neuropils. Netrins are axonal guidance molecules that are conserved regulators of embryonic nerve cord patterning. However, whether they contribute to MB morphogenesis has not yet been evaluated. Here, we find that Netrin-B (NetB) is highly expressed in the MB lobes, regulating lobe length through genetic interactions with the receptors Frazzled and Uncoordinated-5 from 24 h after pupal formation onwards. We observe that overexpression of NetB causes severe β lobe fusion in the MB, which is similar to the MB defects seen in the Drosophila model of fragile X syndrome (FXS). Our results further show that fragile-X mental retardation protein FMRP inhibits the translational activity of human ortholog Netrin-1 (NTN1). Knock-down of NetB significantly rescues the MB defects and ameliorates deficits in the learning and memory in FXS model Drosophila. These results indicate a critical role for NetB in MB lobe extension and identify NetB as a novel target of FMRP which contributes to learning and memory.
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spelling doaj.art-2b3d2f2b54624d96940367adb2ed9d832022-12-21T23:36:41ZengBMCMolecular Brain1756-66062019-05-0112111110.1186/s13041-019-0472-1Drosophila Netrin-B controls mushroom body axon extension and regulates courtship-associated learning and memory of a Drosophila fragile X syndrome modelHuaixing Kang0Juan Zhao1Xuan Jiang2Guangxu Li3Wen Huang4Huili Cheng5Ranhui Duan6Center for Medical Genetics, School of Life Sciences, Central South UniversityCenter for Medical Genetics, School of Life Sciences, Central South UniversityCenter for Medical Genetics, School of Life Sciences, Central South UniversityCenter for Medical Genetics, School of Life Sciences, Central South UniversityCenter for Medical Genetics, School of Life Sciences, Central South UniversityChangchun Children’ HospitalCenter for Medical Genetics, School of Life Sciences, Central South UniversityAbstract Mushroom body (MB) is a prominent structure essential for olfactory learning and memory in the Drosophila brain. The development of the MB involves the appropriate guidance of axon lobes and sister axon branches. Appropriate guidance that accurately shapes MB development requires the integration of various guidance cues provided by a series of cell types, which guide axons to reach their final positions within the MB neuropils. Netrins are axonal guidance molecules that are conserved regulators of embryonic nerve cord patterning. However, whether they contribute to MB morphogenesis has not yet been evaluated. Here, we find that Netrin-B (NetB) is highly expressed in the MB lobes, regulating lobe length through genetic interactions with the receptors Frazzled and Uncoordinated-5 from 24 h after pupal formation onwards. We observe that overexpression of NetB causes severe β lobe fusion in the MB, which is similar to the MB defects seen in the Drosophila model of fragile X syndrome (FXS). Our results further show that fragile-X mental retardation protein FMRP inhibits the translational activity of human ortholog Netrin-1 (NTN1). Knock-down of NetB significantly rescues the MB defects and ameliorates deficits in the learning and memory in FXS model Drosophila. These results indicate a critical role for NetB in MB lobe extension and identify NetB as a novel target of FMRP which contributes to learning and memory.http://link.springer.com/article/10.1186/s13041-019-0472-1Mushroom body (MB)Netrin-B (NetB)Axon extensionFragile X syndrome (FXS)
spellingShingle Huaixing Kang
Juan Zhao
Xuan Jiang
Guangxu Li
Wen Huang
Huili Cheng
Ranhui Duan
Drosophila Netrin-B controls mushroom body axon extension and regulates courtship-associated learning and memory of a Drosophila fragile X syndrome model
Molecular Brain
Mushroom body (MB)
Netrin-B (NetB)
Axon extension
Fragile X syndrome (FXS)
title Drosophila Netrin-B controls mushroom body axon extension and regulates courtship-associated learning and memory of a Drosophila fragile X syndrome model
title_full Drosophila Netrin-B controls mushroom body axon extension and regulates courtship-associated learning and memory of a Drosophila fragile X syndrome model
title_fullStr Drosophila Netrin-B controls mushroom body axon extension and regulates courtship-associated learning and memory of a Drosophila fragile X syndrome model
title_full_unstemmed Drosophila Netrin-B controls mushroom body axon extension and regulates courtship-associated learning and memory of a Drosophila fragile X syndrome model
title_short Drosophila Netrin-B controls mushroom body axon extension and regulates courtship-associated learning and memory of a Drosophila fragile X syndrome model
title_sort drosophila netrin b controls mushroom body axon extension and regulates courtship associated learning and memory of a drosophila fragile x syndrome model
topic Mushroom body (MB)
Netrin-B (NetB)
Axon extension
Fragile X syndrome (FXS)
url http://link.springer.com/article/10.1186/s13041-019-0472-1
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