title: Uncovering Notch pathway in the parasitic flatworm Schistosoma mansoni.
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.
authors.affiliation: Núcleo de Pesquisa em Ciências Exatas e Tecnológicas, Universidade de Franca, Franca, Avenida, Dr Armando Salles de Oliveira, 201 Franca, SP, Brazil. lizandra.magalhaes@unifran.edu.br.|Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. lizandra.magalhaes@unifran.edu.br.
authors.forename: Lizandra G
authors.initials: LG
authors.lastname: Magalhães
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.|Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, Patos de Minas, MG, Brazil.
authors.forename: Enyara R
authors.initials: ER
authors.lastname: Morais
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Carla B
authors.initials: CB
authors.lastname: Machado
authors.affiliation: Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, Patos de Minas, MG, Brazil.
authors.forename: Matheus S
authors.initials: MS
authors.lastname: Gomes
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Fernanda J
authors.initials: FJ
authors.lastname: Cabral
authors.affiliation: Núcleo de Pesquisa em Ciências Exatas e Tecnológicas, Universidade de Franca, Franca, Avenida, Dr Armando Salles de Oliveira, 201 Franca, SP, Brazil.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Souza
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Cláudia S
authors.initials: CS
authors.lastname: Soares
authors.affiliation: Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil.
authors.forename: Renata G
authors.initials: RG
authors.lastname: Sá
authors.affiliation: Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil.
authors.forename: William
authors.initials: W
authors.lastname: Castro-Borges
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Vanderlei
authors.initials: V
authors.lastname: Rodrigues
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000235:genetics; D000818:Animals; D019295:Computational Biology; D003959:Diamines / Q000494:pharmacology; D005260:Female; D049751:Genome, Helminth / Q000235:genetics*; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008018:Life Cycle Stages / Q000187:drug effects; D008297:Male; D008807:Mice, Inbred BALB C; D010063:Ovum / Q000187:drug effects; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D012550:Schistosoma mansoni / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D012555:Schistosomiasis mansoni / Q000469:parasitology*; D015398:Signal Transduction; D012908:Snails; D013844:Thiazoles / Q000494:pharmacology; D059467:Transcriptome
chemical_list: C000612000:24-diamino-5-phenylthiazole; D003959:Diamines; D015801:Helminth Proteins; D051880:Receptors, Notch; D013844:Thiazoles; D053829:Amyloid Precursor Protein Secretases
keywords: Gamma-secretase complex; Notch pathway; Schistosoma mansoni