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Autonomous and non-cell autonomous role of cilia in structural birth defects in mice.
Francis, Richard J B; San Agustin, Jovenal T; Szabo Rogers, Heather L; Cui, Cheng; Jonassen, Julie A; Eguether, Thibaut; Follit, John A; Lo, Cecilia W; Pazour, Gregory J.
Afiliación
  • Francis RJB; Department of Developmental Biology, University of Pittsburgh, Rangos Research Center, Pittsburgh, Pennsylvania, United States of America.
  • San Agustin JT; Discipline of Biomedical Sciences and Molecular Biology; College of Public Health, Medical and Veterinary Science, James Cook University, Townsville, Australia.
  • Szabo Rogers HL; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States of America.
  • Cui C; Department of Developmental Biology, University of Pittsburgh, Rangos Research Center, Pittsburgh, Pennsylvania, United States of America.
  • Jonassen JA; Center for Craniofacial Regeneration, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
  • Eguether T; Department of Developmental Biology, University of Pittsburgh, Rangos Research Center, Pittsburgh, Pennsylvania, United States of America.
  • Follit JA; Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States of America.
  • Lo CW; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States of America.
  • Pazour GJ; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States of America.
PLoS Biol ; 21(12): e3002425, 2023 Dec.
Article en En | MEDLINE | ID: mdl-38079449
Ciliopathies are associated with wide spectrum of structural birth defects (SBDs), indicating important roles for cilia in development. Here, we provide novel insights into the temporospatial requirement for cilia in SBDs arising from deficiency in Ift140, an intraflagellar transport (IFT) protein regulating ciliogenesis. Ift140-deficient mice exhibit cilia defects accompanied by wide spectrum of SBDs including macrostomia (craniofacial defects), exencephaly, body wall defects, tracheoesophageal fistula (TEF), randomized heart looping, congenital heart defects (CHDs), lung hypoplasia, renal anomalies, and polydactyly. Tamoxifen inducible CAGGCre-ER deletion of a floxed Ift140 allele between E5.5 to 9.5 revealed early requirement for Ift140 in left-right heart looping regulation, mid to late requirement for cardiac outflow septation and alignment, and late requirement for craniofacial development and body wall closure. Surprisingly, CHD were not observed with 4 Cre drivers targeting different lineages essential for heart development, but craniofacial defects and omphalocele were observed with Wnt1-Cre targeting neural crest and Tbx18-Cre targeting epicardial lineage and rostral sclerotome through which trunk neural crest cells migrate. These findings revealed cell autonomous role of cilia in cranial/trunk neural crest-mediated craniofacial and body wall closure defects, while non-cell autonomous multi-lineage interactions underlie CHD pathogenesis, revealing unexpected developmental complexity for CHD associated with ciliopathies.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Ciliopatías / Cardiopatías Congénitas Límite: Animals Idioma: En Revista: PLoS Biol Asunto de la revista: BIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Ciliopatías / Cardiopatías Congénitas Límite: Animals Idioma: En Revista: PLoS Biol Asunto de la revista: BIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos