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

19 Citations (Scopus)
165 Downloads (Pure)


Mutations of the protocadherins, FAT4 and DCHS1, result in Van Maldergem’s syndrome characterized, in part, by craniofacial abnormalities. Here we analyse the role of Dchs1-Fat4 signalling during osteoblast differentiation. 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 that Taz-Runx2 complexes is altered in Dchs1/Fat4 mutant osteoblasts. In conclusion, these data identify Dchs1-Fat4 as a new signaling pathway in osteoblast differentiation, reveal its critical role within the early Runx2 progenitors, and identify distinct requirements for Yap and Taz during osteoblast differentiation.
Original languageEnglish
Article numberdev176776
JournalDevelopment (Cambridge)
Issue number14
Early online date29 Jul 2019
Publication statusPublished - Jul 2019


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


Dive into the research topics of 'Dchs1-fat4 regulation of osteogenic differentiation in mouse'. Together they form a unique fingerprint.

Cite this