OBJECTIVE: Tinagl1 has a weak genetic association with craniosynostosis, but its functions in cartilage and bone development are unknown. Knockdown of Tinagl1 in zebrafish embryos allowed an initial characterization of its potential effects on craniofacial cartilage development and a test of whether these effects could involve Wnt signaling. RESULTS: Tinagl1 knockdown resulted in dose-dependent reductions and defects in ventral pharyngeal arch cartilages as well as the ethmoid plate, a zebrafish correlate to the palate. These defects could be correlated to reduced numbers of cranial neural crest cells in the pharyngeal arches and could be reproduced with comanipulation of Tinagl1 and Wnt3a by morpholino-based knockdown. CONCLUSIONS: These results suggest that Tinagl1 is required early in the proliferation or migration of cranial neural crest cells and that its effects are mediated via Wnt3a signaling. Because Wnt3a is among the Wnts that contribute to nonsyndromic cleft lip and cleft palate in mouse and man, further investigation of Tinagl1 may help to elucidate mechanisms underlying these disorders.
OBJECTIVE:Tinagl1 has a weak genetic association with craniosynostosis, but its functions in cartilage and bone development are unknown. Knockdown of Tinagl1 in zebrafish embryos allowed an initial characterization of its potential effects on craniofacial cartilage development and a test of whether these effects could involve Wnt signaling. RESULTS:Tinagl1 knockdown resulted in dose-dependent reductions and defects in ventral pharyngeal arch cartilages as well as the ethmoid plate, a zebrafish correlate to the palate. These defects could be correlated to reduced numbers of cranial neural crest cells in the pharyngeal arches and could be reproduced with comanipulation of Tinagl1 and Wnt3a by morpholino-based knockdown. CONCLUSIONS: These results suggest that Tinagl1 is required early in the proliferation or migration of cranial neural crest cells and that its effects are mediated via Wnt3a signaling. Because Wnt3a is among the Wnts that contribute to nonsyndromic cleft lip and cleft palate in mouse and man, further investigation of Tinagl1 may help to elucidate mechanisms underlying these disorders.
Authors: Hye-Jung E Chun; Pascal D Johann; Katy Milne; Marc Zapatka; Annette Buellesbach; Naveed Ishaque; Murat Iskar; Serap Erkek; Lisa Wei; Basile Tessier-Cloutier; Jake Lever; Emma Titmuss; James T Topham; Reanne Bowlby; Eric Chuah; Karen L Mungall; Yussanne Ma; Andrew J Mungall; Richard A Moore; Michael D Taylor; Daniela S Gerhard; Steven J M Jones; Andrey Korshunov; Manfred Gessler; Kornelius Kerl; Martin Hasselblatt; Michael C Frühwald; Elizabeth J Perlman; Brad H Nelson; Stefan M Pfister; Marco A Marra; Marcel Kool Journal: Cell Rep Date: 2019-11-07 Impact factor: 9.423
Authors: Laura S Bisogno; Jun Yang; Brian D Bennett; James M Ward; Lantz C Mackey; Lois A Annab; Pierre R Bushel; Sandeep Singhal; Shepherd H Schurman; Jung S Byun; Anna María Nápoles; Eliseo J Pérez-Stable; David C Fargo; Kevin Gardner; Trevor K Archer Journal: Sci Adv Date: 2020-11-20 Impact factor: 14.136