I Crespo-Enriquez
Dchs1-Fat4 regulation of osteogenic differentiation in mouse
Crespo-Enriquez, I; Hodgson, T; Zakaria, S; Cadoni, E; Shah, M; Allen, S; Al-Krishali, A; Mao, Y; Yiu, A; Villagomez-Olea, G; Petzold, J; Pitsillides, A A; Irvine, K; Francis-West, P
Authors
T Hodgson
S Zakaria
E Cadoni
M Shah
S Allen
A Al-Krishali
Y Mao
A Yiu
G Villagomez-Olea
J Petzold
A A Pitsillides
K Irvine
P Francis-West
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.
Citation
Crespo-Enriquez, I., Hodgson, T., Zakaria, S., Cadoni, E., Shah, M., Allen, S., …Francis-West, P. (2019). Dchs1-Fat4 regulation of osteogenic differentiation in mouse. Development, 146, https://doi.org/10.1242/dev.176776
Journal Article Type | Article |
---|---|
Acceptance Date | Jun 20, 2019 |
Publication Date | Jul 29, 2019 |
Deposit Date | Aug 1, 2019 |
Publicly Available Date | Jul 29, 2020 |
Journal | DEVELOPMENT |
Print ISSN | 1011-6370 |
Electronic ISSN | 1461-7072 |
Publisher | The Company of Biologists |
Peer Reviewed | Peer Reviewed |
Volume | 146 |
DOI | https://doi.org/10.1242/dev.176776 |
Public URL | https://rvc-repository.worktribe.com/output/1381035 |
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