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Uncovering Notch pathway in the parasitic flatworm Schistosoma mansoni

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Abstract

Several signaling molecules that govern development in higher animals have been identified in the parasite Schistosoma mansoni, including the transforming growth factor β, protein tyrosine kinases, nuclear hormone receptors, among others. The Notch pathway is a highly conserved signaling mechanism which is involved in a wide variety of developmental processes including embryogenesis and oogenesis in worms and flies. Here we aimed to provide the molecular reconstitution of the Notch pathway in S. mansoni using the available transcriptome and genome databases. Our results also revealed the presence of the transcripts coded for SmNotch, SmSu(H), SmHes, and the gamma-secretase complex (SmNicastrin, SmAph-1, and SmPen-2), throughout all the life stages analyzed. Besides, it was observed that the viability and separation of adult worm pairs were not affected by treatment with N-[N(3,5)-difluorophenacetyl)-L-Alanyl]-S-phenylglycine t-butyl ester (DAPT), a Notch pathway inhibitor. Moreover, DAPT treatment decreased the production of phenotypically normal eggs and arrested their development in culture. Our results also showed a significant decrease in SmHes transcript levels in both adult worms and eggs treated with DAPT. These results provide, for the first time, functional validation of the Notch pathway in S. mansoni and suggest its involvement in parasite oogenesis and embryogenesis. Given the complexity of the Notch pathway, further experiments shall highlight the full repertoire of Notch-mediated cellular processes throughout the S. mansoni life cycle.

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Acknowledgments

This study received financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil—FAPESP (Processes: 2003/04295-3) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil—CAPES. We also acknowledge Elenice Aparecida Macedo and Olinda Mara Brigatto for their technical support. We thank the Wellcome Trust Sanger Institute and The Institute for Genomic Research for allowing the use of their sequences that are available via GeneDB.

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  1. Lizandra G. Magalhães

    Present address: Núcleo de Pesquisa em Ciências Exatas e Tecnológicas, Universidade de Franca, Franca, Avenida, Dr Armando Salles de Oliveira, 201 Franca, SP, Brazil

Authors and Affiliations

  1. Núcleo de Pesquisa em Ciências Exatas e Tecnológicas, Universidade de Franca, Franca, Avenida, Dr Armando Salles de Oliveira, 201 Franca, SP, Brazil

    Julia M. Souza

  2. Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil

    Lizandra G. Magalhães, Enyara R. Morais, Carla B. Machado, Fernanda J. Cabral, Cláudia S. Soares & Vanderlei Rodrigues

  3. Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, Patos de Minas, MG, Brazil

    Enyara R. Morais & Matheus S. Gomes

  4. Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil

    Renata G. Sá & William Castro-Borges

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  1. Lizandra G. Magalhães
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Correspondence to Lizandra G. Magalhães.

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Magalhães, L.G., Morais, E.R., Machado, C.B. et al. Uncovering Notch pathway in the parasitic flatworm Schistosoma mansoni . Parasitol Res 115, 3951–3961 (2016). https://doi.org/10.1007/s00436-016-5161-8

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