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Dchs1-Fat4 regulation of osteogenic differentiation in mouse.
Development. 2019 07 29; 146(14)D

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.

Authors+Show Affiliations

Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, Floor 27, Guy's Tower, London SE1 9RT, UK.Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, Floor 27, Guy's Tower, London SE1 9RT, UK.Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, Floor 27, Guy's Tower, London SE1 9RT, UK.Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, Floor 27, Guy's Tower, London SE1 9RT, UK.Comparative Biomedical Sciences, Royal Veterinary College, Camden, London, NW1 0TU, UK.Comparative Biomedical Sciences, Royal Veterinary College, Camden, London, NW1 0TU, UK.Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, Floor 27, Guy's Tower, London SE1 9RT, UK.Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, Floor 27, Guy's Tower, London SE1 9RT, UK.Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, Floor 27, Guy's Tower, London SE1 9RT, UK.Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, Floor 27, Guy's Tower, London SE1 9RT, UK.Comparative Biomedical Sciences, Royal Veterinary College, Camden, London, NW1 0TU, UK.Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31358536

Citation

Crespo-Enriquez, Ivan, et al. "Dchs1-Fat4 Regulation of Osteogenic Differentiation in Mouse." Development (Cambridge, England), vol. 146, no. 14, 2019.
Crespo-Enriquez I, Hodgson T, Zakaria S, et al. Dchs1-Fat4 regulation of osteogenic differentiation in mouse. Development. 2019;146(14).
Crespo-Enriquez, I., Hodgson, T., Zakaria, S., Cadoni, E., Shah, M., Allen, S., Al-Khishali, A., Mao, Y., Yiu, A., Petzold, J., Villagomez-Olea, G., Pitsillides, A. A., Irvine, K. D., & Francis-West, P. (2019). Dchs1-Fat4 regulation of osteogenic differentiation in mouse. Development (Cambridge, England), 146(14). https://doi.org/10.1242/dev.176776
Crespo-Enriquez I, et al. Dchs1-Fat4 Regulation of Osteogenic Differentiation in Mouse. Development. 2019 07 29;146(14) PubMed PMID: 31358536.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dchs1-Fat4 regulation of osteogenic differentiation in mouse. AU - Crespo-Enriquez,Ivan, AU - Hodgson,Tina, AU - Zakaria,Sana, AU - Cadoni,Erika, AU - Shah,Mittal, AU - Allen,Stephen, AU - Al-Khishali,Ayman, AU - Mao,Yaopan, AU - Yiu,Angela, AU - Petzold,Jonna, AU - Villagomez-Olea,Guillermo, AU - Pitsillides,Andrew A, AU - Irvine,Kenneth D, AU - Francis-West,Philippa, Y1 - 2019/07/29/ PY - 2019/02/09/received PY - 2019/06/20/accepted PY - 2019/7/31/entrez PY - 2019/7/31/pubmed PY - 2020/7/7/medline KW - Dchs1-Fat4 KW - Osteoblast KW - Runx2 KW - Yap/Taz JF - Development (Cambridge, England) JO - Development VL - 146 IS - 14 N2 - 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. SN - 1477-9129 UR - https://www.unboundmedicine.com/medline/citation/31358536/Dchs1_Fat4_regulation_of_osteogenic_differentiation_in_mouse_ L2 - http://dev.biologists.org/cgi/pmidlookup?view=long&pmid=31358536 DB - PRIME DP - Unbound Medicine ER -