Autonomous and non-cell autonomous role of cilia in structural birth defects in mice
Francis, Richard J.B., Agustin, Jovenal T.San, Rogers, Heather L.Szabo, Cui, Cheng, Jonassen, Julie A., Eguether, Thibaut, Follit, John A., Lo, Cecilia W., and Pazour, Gregory (2023) Autonomous and non-cell autonomous role of cilia in structural birth defects in mice. PLoS Biology, 21 (12). e3002425.
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Abstract
Ciliopathies are associated with wide spectrum of structral birth defects (SBDs), indicating impoartant roles for cilia in decelopment , 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.
| Item ID: | 81501 |
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| Item Type: | Article (Research - C1) |
| ISSN: | 1545-7885 |
| Copyright Information: | © 2023 Francis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Date Deposited: | 04 Jan 2024 00:22 |
| FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320101 Cardiology (incl. cardiovascular diseases) @ 50% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3215 Reproductive medicine > 321501 Foetal development and medicine @ 50% |
| SEO Codes: | 20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 50% 20 HEALTH > 2005 Specific population health (excl. Indigenous health) > 200506 Neonatal and child health @ 50% |
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