AUTHOR=Quarto Natalina , Shailendra Siny , Meyer Nathaniel P. , Menon Siddharth , Renda Andrea , Longaker Michael T. 

TITLE=Twist1-Haploinsufficiency Selectively Enhances the Osteoskeletal Capacity of Mesoderm-Derived Parietal Bone Through Downregulation of Fgf23

JOURNAL=Frontiers in Physiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.01426

DOI=10.3389/fphys.2018.01426

ISSN=1664-042X

ABSTRACT=<p>Craniofacial development is a program exquisitely orchestrated by tissue contributions and regulation of genes expression. The basic helix–loop–helix (bHLH) transcription factor Twist1 expressed in the skeletal mesenchyme is a key regulator of craniofacial development playing an important role during osteoskeletogenesis. This study investigates the postnatal impact of <italic>Twist1</italic> haploinsufficiency on the osteoskeletal ability and regeneration on two calvarial bones arising from tissues of different embryonic origin: the neural crest-derived frontal and the mesoderm-derived parietal bones. We show that <italic>Twist1</italic> haplonsufficiency as well <italic>Twist1</italic>-sh-mediated silencing selectively enhanced osteogenic and tissue regeneration ability of mesoderm-derived bones. Transcriptomic profiling, gain-and loss-of-function experiments revealed that <italic>Twist1</italic> haplonsufficiency triggers its selective activity on mesoderm-derived bone through a sharp downregulation of the bone-derived hormone <italic>Fgf23</italic> that is upregulated exclusively in wild-type parietal bone.</p>