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Updated: Dec 25, 2025
Dissection and Immunofluorescent Staining of Mushroom Body and Photoreceptor Neurons in Adult Drosophila melanogaster Brains
Published on: November 6, 2017
Mutations associated with human neural tube defects display disrupted planar cell polarity in Drosophila
Ashley C Humphries1,2,3, Sonali Narang1,2,3, Marek Mlodzik1,2,3
1Department of Cell, Developmental and Regenerative Biology, New York, United States.
Abstract:
Planar cell polarity (PCP) and neural tube defects (NTDs) are linked, with a subset of NTD patients found to harbor mutations in PCP genes, but there is limited data on whether these mutations disrupt PCP signaling in vivo. The core PCP gene Van Gogh (Vang), Vangl1/2 in mammals, is the most specific for PCP. We thus addressed potential causality of NTD-associated Vangl1/2 mutations, from either mouse or human patients, in Drosophila allowing intricate analysis of the PCP pathway. Introducing the respective mammalian mutations into Drosophila Vang revealed defective phenotypic and functional behaviors, with changes to Vang localization, post-translational modification, and mechanistic function, such as its ability to interact with PCP effectors. Our findings provide mechanistic insight into how different mammalian mutations contribute to developmental disorders and strengthen the link between PCP and NTD. Importantly, analyses of the human mutations revealed that each is a causative factor for the associated NTD.
Insights
Mutations in planar cell polarity (PCP) genes, like Vangl1/2, can cause neural tube defects (NTDs). This study used Drosophila to show how these mutations disrupt PCP signaling, confirming their causal role in NTDs.
Area of Science:
- Developmental Biology
- Genetics
- Cell Biology
Background:
- Planar cell polarity (PCP) signaling is crucial for tissue development.
- Mutations in PCP genes are linked to neural tube defects (NTDs).
- The specific role of NTD-associated Vangl1/2 mutations in vivo remains unclear.
Purpose of the Study:
- To investigate the in vivo causality of mammalian Vangl1/2 mutations in NTDs.
- To elucidate the mechanistic impact of these mutations on PCP pathway function.
- To strengthen the link between PCP disruption and NTD pathogenesis.
Main Methods:
- Utilized Drosophila melanogaster as a model organism for detailed PCP pathway analysis.
- Introduced mammalian Vangl1/2 mutations into the Drosophila Vang gene.
- Assessed phenotypic and functional consequences of introduced mutations on Vang protein behavior.
Main Results:
- Mammalian Vangl1/2 mutations introduced into Drosophila Vang caused defective phenotypes.
- Mutations altered Vang protein localization, post-translational modification, and effector interactions.
- Each analyzed human mutation was confirmed as a causative factor for associated NTDs.
Conclusions:
- Provides mechanistic insights into how Vangl1/2 mutations contribute to developmental disorders.
- Establishes a direct link between specific Vangl1/2 mutations and NTD etiology.
- Highlights the utility of Drosophila for studying human disease-associated genetic mutations.
