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Nubp2 is required for cranial neural crest survival in the mouse.
DiStasio, Andrew; Paulding, David; Chaturvedi, Praneet; Stottmann, Rolf W.
Afiliação
  • DiStasio A; Division of Human Genetics, OH, 45229, USA.
  • Paulding D; Division of Human Genetics, OH, 45229, USA.
  • Chaturvedi P; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, OH, 45229, USA.
  • Stottmann RW; Division of Human Genetics, OH, 45229, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, OH, 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA; Shriner's Hospital for Children - Cincinnati, Cincinnati,
Dev Biol ; 458(2): 189-199, 2020 02 15.
Article em En | MEDLINE | ID: mdl-31733190
The N-ethyl-N-nitrosourea (ENU) ←forward genetic screen is a useful tool for the unbiased discovery of novel mechanisms regulating developmental processes. We recovered the dorothy mutation in such a screen designed to recover recessive mutations affecting craniofacial development in the mouse. Dorothy embryos die prenatally and exhibit many striking phenotypes commonly associated with ciliopathies, including a severe midfacial clefting phenotype. We used exome sequencing to discover a missense mutation in nucleotide binding protein 2 (Nubp2) to be causative. This finding was confirmed by a complementation assay with the dorothy allele and an independent Nubp2 null allele (Nubp2null). We demonstrated that Nubp2 is indispensable for embryogenesis. NUBP2 is implicated in both the cytosolic iron/sulfur cluster assembly pathway and negative regulation of ciliogenesis. Conditional ablation of Nubp2 in the neural crest lineage with Wnt1-cre recapitulates the dorothy craniofacial phenotype. Using this model, we found that the proportion of ciliated cells in the craniofacial mesenchyme was unchanged, and that markers of the SHH, FGF, and BMP signaling pathways are unaltered. Finally, we show evidence that the phenotype results from a marked increase in apoptosis within the craniofacial mesenchyme.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Ligação ao GTP / Crista Neural Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Ligação ao GTP / Crista Neural Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article