AUTHOR=Ha Nayoung , Sun Jian , Bian Qian , Wu Dandan , Wang Xudong 

TITLE=Hdac4 Regulates the Proliferation of Neural Crest-Derived Osteoblasts During Murine Craniofacial Development

JOURNAL=Frontiers in Physiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.819619

DOI=10.3389/fphys.2022.819619

ISSN=1664-042X

ABSTRACT=<p>Craniofacial development involves the regulation of a compendium of transcription factors, signaling molecules, and epigenetic regulators. Histone deacetylases (HDACs) are involved in the regulation of cell proliferation, differentiation, and homeostasis across a wide range of tissues, including the brain and the cardiovascular, muscular, and skeletal systems. However, the functional role of <italic>Hdac4</italic> during craniofacial development remains unclear. In this study, we investigated the effects of knocking out <italic>Hdac4</italic> on craniofacial skeletal development by conditionally disrupting the <italic>Hdac4</italic> gene in cranial neural crest cells (CNCCs) using Cre-mediated recombination. Mice deficient for <italic>Hdac4</italic> in CNCC-derived osteoblasts demonstrated a dramatic decrease in frontal bone formation. <italic>In vitro</italic>, pre-osteoblasts (MC3T3-E1 cells) lacking <italic>Hdac4</italic> exhibited reduced proliferative activity in association with the dysregulation of cell cycle-related genes. These findings suggested that <italic>Hdac4</italic> acts, at least in part, as a regulator of craniofacial skeletal development by positively regulating the proliferation of CNCC-derived osteoblasts.</p>