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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.   Electronic supplementary material  The online version of this article (10.1186/s13041-019-0472-1) contains supplementary material, which is available to authorized users.

molecular brain

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