Skeletal Cell YAP And TAZ Redundantly Promote Bone Development By Regulation Of Collagen I Expression And Organization

Article

Abstract

The functions of the transcriptional co-activators YAP and TAZ in bone are controversial. Each has been observed to either promote or inhibit osteogenesis in vitro, while their roles in bone development are unknown. Here we report that combinatorial YAP/TAZ deletion from skeletal cells in mice caused osteogenesis imperfecta with severity dependent on targeted cell lineage and allele dosage. Osteocyte-conditional deletion impaired bone accrual and matrix collagen, while allele dosage-dependent deletion from all osteogenic lineage cells caused spontaneous fractures, with neonatal lethality only in dual homozygous knockouts. We identified putative target genes whose mutation in humans causes osteogenesis imperfecta and which contain promoter-proximate binding domains for the YAP/TAZ co-effector, TEAD4. Two candidates, Col1a1 and SerpinH1, exhibited reduced expression upon either YAP/TAZ deletion or YAP/TAZ-TEAD inhibition by verteporfin. Together, these data demonstrate that YAP and TAZ redundantly promote bone matrix development and implicate YAP/TAZ-mediated transcriptional regulation of collagen in osteogenesis imperfecta.

Attributes

Attribute NameValues
Creator
  • Christopher D. Kagelman

  • Devon E. Mason

  • James H. Dawahare

  • Genevieve D. Vigil

  • Scott S. Howard

  • Teresita M. Bellido

  • Alexander G. Robling

  • Joel Boerckel

Journal or Work Title
  • bioRxiv

Number of Pages
  • 40

Publication Date
  • 2017-05

Publisher
  • Cold Spring Harbor

Date Created
  • 2018-10-26

Language
  • English

Departments and Units
Record Visibility and Access Public
Content License
  • All rights reserved

Digital Object Identifier

doi:10.1101/143982

This DOI is the best way to cite this article.