Dysregulated BMP signaling through ACVR1 impairs digit joint development in fibrodysplasia ossificans progressiva (FOP).

Developmental Biology
O Will TowlerEileen M Shore

Abstract

The development of joints in the mammalian skeleton depends on the precise regulation of multiple interacting signaling pathways including the bone morphogenetic protein (BMP) pathway, a key regulator of joint development, digit patterning, skeletal growth, and chondrogenesis. Mutations in the BMP receptor ACVR1 cause the rare genetic disease fibrodysplasia ossificans progressiva (FOP) in which extensive and progressive extra-skeletal bone forms in soft connective tissues after birth. These mutations, which enhance BMP-pSmad1/5 pathway activity to induce ectopic bone, also affect skeletal development. FOP can be diagnosed at birth by symmetric, characteristic malformations of the great toes (first digits) that are associated with decreased joint mobility, shortened digit length, and absent, fused, and/or malformed phalanges. To elucidate the role of ACVR1-mediated BMP signaling in digit skeletal development, we used an Acvr1R206H/+;Prrx1-Cre knock-in mouse model that mimics the first digit phenotype of human FOP. We have determined that the effects of increased Acvr1-mediated signaling by the Acvr1R206H mutation are not limited to the first digit but alter BMP signaling, Gdf5+ joint progenitor cell localization, and joint devel...Continue Reading

References

Jan 1, 1967·Humangenetik·W TünteG V Knorre
May 26, 1999·Developmental Dynamics : an Official Publication of the American Association of Anatomists·C HealyP T Sharpe
Jul 12, 2002·Genesis : the Journal of Genetics and Development·Malcolm LoganClifford J Tabin
Sep 8, 2004·Journal of Cellular Biochemistry·Byeong S Yoon, Karen M Lyons
Oct 20, 2004·PLoS Biology·Ryan B RountreeDavid M Kingsley
Nov 29, 2005·Foot & Ankle International·Richard J HarrisonSean P Scully
Jun 29, 2006·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Dylan SweetmanTamas Dalmay
Dec 30, 2006·PLoS Genetics·Amitabha BandyopadhyayClifford J Tabin
Dec 18, 2007·Annals of the New York Academy of Sciences·Eiki KoyamaMaurizio Pacifici
Mar 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Takayuki SuzukiJohn F Fallon
May 3, 2008·Pediatrics·Frederick S KaplanEileen M Shore
Dec 1, 2010·Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association·Yasuharu NakashimaYukihide Iwamoto
May 4, 2011·Genesis : the Journal of Genetics and Development·Laura W GamerVicki Rosen
Apr 18, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Salin A ChakkalakalEileen M Shore
Nov 23, 2013·Nucleic Acids Research·Lorna RichardsonChris Armit
Apr 11, 2014·Seminars in Cell & Developmental Biology·Emanuele PignattiAimée Zuniga
Jul 19, 2014·Developmental Biology·Jacqueline L NorrieSteven A Vokes
Nov 22, 2014·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Diana RigueurKaren M Lyons
Sep 4, 2015·Science Translational Medicine·Sarah J HatsellAris N Economides
Sep 20, 2015·BMC Biology·Uwe KlammertJoachim Nickel
Feb 21, 2016·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Salin A ChakkalakalEileen M Shore
Jun 14, 2016·Cell Reports·Yulia ShwartzElazar Zelzer
Oct 25, 2016·Seminars in Cell & Developmental Biology·Rebekah S Decker
May 6, 2017·European Journal of Medical Genetics·O Will TowlerFrederick S Kaplan
Feb 23, 2018·Development·Pratik Narendra Pratap SinghAmitabha Bandyopadhyay
Mar 12, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Laura HildebrandKatja Stange
Mar 5, 2020·Development·Jake Cornwall Scoones, Tom W Hiscock

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Citations

May 12, 2021·American Journal of Medical Genetics. Part a·Diana Martín-GarcíaFrederick S Kaplan
Jun 17, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Oscar Will Towler, Eileen M Shore

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