Dchs1-fat4 regulation of osteogenic differentiation in mouse

Ivan Crespo-Enriquez, Tina Hodgson, Sana Zakaria, Erika Cadoni, Mittal Shah, Stephen Allen, Ayman Al-Khishali, Yaopan Mao, Angela Yiu, Jonna Petzold, Guillermo Villagomez-Olea, Andrew A. Pitsillides, Kenneth D. Irvine, Philippa Francis-West

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageEnglish (US)
Article numberdev176776
JournalDevelopment (Cambridge)
Issue number14
StatePublished - Jul 2019

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology


  • Dchs1-Fat4
  • Osteoblast
  • Runx2
  • Yap/Taz


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