Crespo-Enriquez, I and Hodgson, T and Zakaria, S and Cadoni, E and Shah, M and Allen, S and Al-Krishali, A and Mao, Y and Yiu, A and Villagomez-Olea, G and Petzold, J and Pitsillides, A A and Irvine, K and Francis-West, P (2019) Dchs1-Fat4 regulation of osteogenic differentiation in mouse. DEVELOPMENT, 146.
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Abstract
In human, mutations of the protocadherins FAT4 and DCHS1 result in Van Maldergem syndrome, which is characterised, in part, by craniofacial abnormalities. Here, we analyse the role of Dchs1-Fat4 signalling during osteoblast differentiation in mouse. We show that Fat4 and Dchs1 mutants mimic the craniofacial phenotype of the human syndrome and that Dchs1-Fat4 signalling is essential for osteoblast differentiation. In Dchs1/Fat4 mutants, proliferation of osteoprogenitors is increased and osteoblast differentiation is delayed. We show that loss of Dchs1-Fat4 signalling is linked to increased Yap-Tead activity and that Yap is expressed and required for proliferation in osteoprogenitors. In contrast, Taz is expressed in more-committed Runx2-expressing osteoblasts, Taz does not regulate osteoblast proliferation and Taz-Tead activity is unaffected in Dchs1/Fat4 mutants. Finally, we show that Yap and Taz differentially regulate the transcriptional activity of Runx2, and that the activity of Yap-Runx2 and Taz-Runx2 complexes is altered in Dchs1/Fat4 mutant osteoblasts. In conclusion, these data identify Dchs1-Fat4 as a signalling pathway in osteoblast differentiation, reveal its crucial role within the early Runx2 progenitors, and identify distinct requirements for Yap and Taz during osteoblast differentiation.
| Item Type: | Article |
|---|---|
| RVC Publication Type: | Research (full) paper |
| DOI: | https://doi.org/10.1242/dev.176776 |
| Departments: | Comparative Biomedical Sciences |
| Research Programmes: | Comparative Physiology & Medicine > Musculoskeletal Biology |
| Depositing User: | RVC Auto-import |
| Date Deposited: | 01 Aug 2019 05:00 |
| Last Modified: | 01 Aug 2019 10:26 |
| URI: | http://researchonline.rvc.ac.uk/id/eprint/12265 |